Increased serum VEGF and b-FGF in Graves’ ophthalmopathy

Background

Graves’ ophthalmopathy (GO) is thought to be an inflammatory disorder of autoimmune background. The aim of this study is to investigate the involvement of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) in patients with Graves’ ophthalmopathy (GO).

Methods

Serum concentrations of VEGF and b-FGF of 48 GO patients, 30 Graves’ hyperthyroid disease (GD) patients without ophthalmopathy, and 30 healthy controls were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Patients with GO were subdivided into two groups according to clinical activity scores (CAS): a score of 3 or less is considered as inactive (CAS?≤?3, inactive GO, n?=?14), and 4 or more is considered active eye disease (CAS?≥?4, active GO; n?=?34). All of the patients with active GO underwent corticosteroid therapy.

Results

The concentrations of serum VEGF and b-FGF were significantly higher in patients with GO and in those with GD than in controls. The serum levels of VEGF and b-FGF in patients with active GO were higher than those in patients with inactive GO and those in GD patients (P?VEGF and b-FGF concentratison were significantly correlated with CAS in GO patients (p?VEGF and b-FGF levels in corticosteroid-responsive patients (CAS decreases ≥3 after treatment) decreased significantly after corticosteroid treatment (P?P?Conclusion The results suggest that serum VEGF and b-FGF levels were increased in patients with active GO and could reflect the degree of ocular inflammatory activity.     

Simultaneous study of matrix metalloproteinases,proinflammatory cytokines,and soluble cytokine receptors in the tears of noninfectious corneal ulcer patients

Background

We investigated the presence of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), proinflammatory cytokines, and soluble cytokine receptors in the tear fluid of patients with noninfectious corneal ulcers in the peripheral cornea.

Methods

The subjects were 20 eyes of 17 patients with peripheral noninfectious corneal ulcers and 20 eyes of 20 volunteers. Tear samples were taken by the Schirmer test I method and the presence of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, and MMP-13) and TIMPs (TIMP-1, TIMP-2, and TIMP-4) were investigated using an MMP antibody array system. The concentrations of proinflammatory cytokines {IL-1β, IL-6, and TNF-α (tumor necrosis factor-alpha)} and soluble cytokine receptors {soluble (s) IL-1R1, sIL-1R2, sIL-2Rα, sIL-4R, sIL-6R, sTNFR1, sTNFR2, s-vascular endothelial growth factor receptor (VEGFR) 1, sVEGFR2, sVEGFR3, and sgp130} were determined using the multiplex bead immunoassay system.

Results

The concentrations of MMP-8 and MMP-9 were significantly up-regulated in the tear fluid of the ulcer patients, whereas TIMPs concentrations did not change. The concentrations of IL-1β, IL-6, sIL-1R2, sIL-6R, sTNFR1, and sTNFR2 were up-regulated in the ulcer patients, whereas sgp130 and sVEGFR1 concentrations significantly decreased.

Conclusions

The presence of some MMPs increased significantly in the patients with peripheral noninfectious corneal ulcers, whereas the presence of TIMPs remained unchanged. Although some proinflammatory cytokines were up-regulated, their antagonists, soluble cytokine receptors, were also up-regulated. It is thus possible that the up-regulation of MMPs disrupts the balance between the MMPs and TIMPs and that this balance may play a pivotal role in the pathophysiology of corneal ulceration.     

Comparison of the efficacy of aflibercept,ranibizumab, and bevacizumab in an RPE/choroid organ culture

Purpose

Anti-VEGF treatment is the therapy of choice in age-related macular degeneration and is also applied in diabetic macular edema or retinal vein occlusion. Recently, aflibercept has been approved for therapeutic use. In this study, we investigate the efficacy of aflibercept in comparison with the VEGF-antagonists ranibizumab and bevacizumab in RPE/choroid organ cultures.

Methods

RPE/choroid organ cultures were prepared from freshly slaughtered pigs’ eyes. Organ cultures were treated with 125 μg/ml aflibercept, ranibizumab, or bevacizumab, and the VEGF content of the supernatant was evaluated over the course of 7 days. Additionally, the minimal concentration of VEGF inhibition was evaluated in organ cultures, measured after 6 h of application.

Results

Aflibercept was able to completely inhibit VEGF detection for 6 h at a minimal concentration of 0.031 μg/ml, in contrast to bevacizumab (3.9 μg/ml) and ranibizumab (0.244 μg/ml). A statistically significant VEGF inhibition compared to control could be found for aflibercept and ranibizumab down to and including 0.031 μg/ml, while bevacizumab was significantly reduced compared to control down to a concentration of 0.244 μg/ml and again at 0.061 μg/ml. Inhibition of VEGF after a single aflibercept application of 125 μg/ml could be found over the course of 7 days, with some VEGF detectable at the 7th day. In contrast, VEGF was detectable after 72 h of ranibizumab treatment and some VEGF could already be found 12 h after bevacizumab treatment.

Conclusions

In conclusion, aflibercept displays a prolonged VEGF inhibition, confirming its effectiveness but also raising concerns about possible side effects of long-term usage.     

Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration

Background

To evaluate the plasma vascular endothelial growth factor (VEGF) levels after one intravitreal injection of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD).

Methods

Twenty-four Japanese with exudative AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation were included. Fourteen patients received an intravitreal injection of aflibercept, and ten patients received an intravitreal injection of ranibizumab. Plasma VEGF levels were evaluated within 7 days before the intravitreal injections and 1 day, 1 week, and 1 month after the intravitreal injection.

Results

In the ranibizumab group, the mean plasma VEGF levels were 245.7?±?233.4 pg/ml before the injection, 246.6?±?304.8 pg/ml after 1 day, 217.8?±?212.9 pg/ml after 1 week, and 260.0?±?290.1 pg/ml after 1 month. The plasma VEGF levels did not decrease significantly in patients in the ranibizumab group at any time point. In the aflibercept group, the mean plasma VEGF levels were 280.0?±?170.3 pg/ml before the intravitreal injection and 8.2?±?12.9 pg/ml after 1 day, 9.1?±?9.1 pg/ml after 1 week, and 41.9?±?41.4 pg/ml after 1 month (p?Conclusion Intravitreally injected aflibercept reduced plasma VEGF over at least 1 month. In contrast, intravitreal injection of ranibizumab did not cause a significant reduction in the plasma VEGF levels.     

Changes of TGF-β2, MMP-2, and TIMP-2 levels in the vitreous of patients with high myopia

Purpose

To investigate the concentrations of transforming growth factor (TGF)-β2, matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-2 in the vitreous of patients with high myopia.

Methods

Twenty-six patients with high myopia (HM) who received vitrectomy for macular retinoschisis or macular hole were enrolled in this prospective study. Twenty-six patients with idiopathic macular hole or macular epiretinal membrane were chosen as a control group. Vitreous samples were obtained during the vitrectomy surgery. The levels of TGF-β2、MMP-2、TIMP-2 in the vitreous samples were measured by enzyme-linked immunosorbent assay. The MMP activity was determined by a fluorometric assay.

Results

There was no significant difference in the vitreous level of TGF-β2 between HM (1.64?±?0.38 ng/ml) and the control group (1.56?±?0.32 ng/ml, p?=?0.56). The vitreous levels of MMP-2 in HM (32.40?±?14.90 ng/ml) were significantly higher than in the control group (21.42?±?6.74 ng/ml, p?MMP-2/TIMP-2 was significantly elevated in the vitreous samples from HM (0.61?±?0.19), compared to the control group (0.48?±?0.11, p?p?Conclusions The elevated MMP/TIMP ratio and MMP activity may play a role in the pathogenesis of human high myopia. Large prospective studies are needed to further investigate the effect of MMPs in the pathogenesis of human high myopia.     

Total IgE and eotaxin (CCL11) contents in tears of patients suffering from seasonal allergic conjunctivitis

Background

To prospectively investigate patients with seasonal allergic conjunctivitis (SAC) during the pollen season and test associations between tears total IgE, eotaxin concentrations, and SAC severity.

Methods

Enrolled patients presented ocular symptoms and clinical signs of SAC at the time of presentation. Ocular itching, hyperaemia, chemosis, eyelid swelling, and tearing were scored, and the sum of these scores was defined as the clinical score. Conjunctival papillae were separately graded. We measured eotaxin concentration in tears by an enzyme-linked immunosorbent assay (ELISA) and total tear IgE by Lacrytest strip.

Results

Among thirty patients (30 eyes), 11 showed neither tear IgE nor tear eotaxin, while 15 out of 19 patients with positive IgE values presented a positive amount of eotaxin in their tears (Fisher’s test: p?IgE, we observed a lower conjunctival papilla grade than in patients whose tears contained some amount of IgE (trend test: p?=?0.032). In the 15 patients whose tear eotaxin concentration was null, tear IgE concentration was 5.3?±?3.5 arbitrary units; in the other 15 patients whose eotaxin was positive, IgE reached 21?±?4.3 arbitrary U (Mann–Whitney: p?p?=?0.008). In contrast, tear IgE concentrations of both groups did not differ statistically significantly (p?=?0.947).

Conclusions

If IgE and eotaxin secreted in tears are major contributors in SAC pathogenesis, they however act at different steps of the process.     

The retinal pigment epithelium (RPE) induces FasL and reduces iNOS and Cox2 in primary monocytes

Purpose

Retinal pigment epithelium (RPE) cells may alter the phenotype of monocytes by soluble factors that may be influenced by stimulation of the RPE. Since RPE cells carry the toll-like receptor-3 (TLR3) that detects and reacts to viral infection through binding of dsRNA we investigated the effects of RPE cells with or without TLR3 stimulation on blood-derived monocytes with respect to regulation of pro-/anti-inflammatory cytokines, anti-angiogenic factors and migratory properties.

Methods

Primary RPE cells were prepared from porcine eyes; monocytes were prepared from porcine blood. TLR3 activation was induced by polyinosinic:polycytidylic acid (Poly I:C). RPE cells were stimulated with Poly I:C in different concentrations for 24 hours and a cell culture supernatant was applied to the monocytes. Expression of CD14 and Fas ligand (FasL) was determined via flow cytometry. The expression of IL-6, IL-1ß, TNFα, Cox2, iNOS and IL-10 was determined via quantitative RT-PCR. Migration was determined using Boyden chamber experiments.

Results

The supernatant of RPE cells, irrespective of TLR3 activation, induced FasL expression in the monocytes. Expression of iNOS and Cox2 was reduced by RPE cells and the reduction of Cox2 but not if iNOS was lost under TLR3 activation. No induction of IL-6, IL-1ß, IL-10 or TNFα by the RPE was seen. TLR3-activated RPE cells induced monocyte migration.

Conclusion

RPE cells induce an upregulation of FasL and a downregulation of iNOS and Cox2 without upregulating inflammatory cytokines, possibly inducing an anti-angiogenic phenotype in the monocytes. This phenotype is still upheld after challenging RPE cells with dsRNA, mimicking a viral infection.     

Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival

Purpose

To investigate the effect of VEGF-C and VEGF-D blockade via soluble VEGFR-3 (sVEGFR-3) on T cell allosensitization, corneal neovascularization, and transplant survival.

Methods

Corneal intrastromal suture placement and allogeneic transplantation were performed on BALB/c mice to evaluate the effect of sVEGFR-3 on corneal neovascularization. Soluble VEGFR-3 trap was injected intraperitoneally to block VEGF-C/D (every other day starting the day of surgery). Immunohistochemical staining of corneal whole mounts was performed using anti-CD31 (PECAM-1) and anti-LYVE-1 antibodies to quantify the levels of hem- and lymphangiogenesis, respectively. Mixed lymphocyte reaction (MLR) was performed to assess indirect and direct host T cell allosensitization and the frequencies of IFN-γ-producing T cells in the draining lymph nodes were assessed using flow cytometry. Graft opacity and survival was evaluated by slit-lamp biomicroscopy.

Results

Treatment with sVEGFR-3 resulted in a significant blockade of lymphangiogenesis 2 weeks post-transplantation and significantly prolonged corneal allograft survival compared to the control group at 8 weeks post-transplantation (87.5 % vs. 50 %), and this was associated with significant reduction in the frequencies of allosensitized T cells and decreased frequencies of IFN-γ–producing CD4 T cells.

Conclusions

Soluble VEGFR-3 suppresses corneal lymphangiogenesis and allograft rejection and may offer a viable therapeutic modality for corneal neovascularization and corneal transplantation.     

Hyperthermia-induced upregulation of vascular endothelial growth factor in retinal pigment epithelial cells is regulated by mitogen-activated protein kinases

Purpose

Localized application of hyperthermia is a potential treatment for retinal diseases. Vascular endothelial growth factor (VEGF) derived from the retinal pigment epithelium (RPE) is implicated in a variety of retinal pathologies. As it has been recently shown that hyperthermia may induce VEGF in the RPE, the aim of this study was to investigate hyperthermia-induced VEGF secretion and the pathways of hyperthermal VEGF upregulation in the RPE.

Material and methods

The human RPE cell line (Arpe-19) was exposed to 40°, 42°, 45° and 50 °C for one, five and 15 min. Cell viability was evaluated using a trypan blue exclusion assay, VEGF secretion was evaluated by an enzyme-linked immunosorbent assay ELISA) and VEGF expression was investigated using a Western blot. Involvement of mitogen-activated protein kinase (MAPK) pathways (ERK1/2, JNK, p38) and transient receptor potential vanilloid (TRPV) channels on VEGF induction was investigated using commercially available inhibitors (U0126, SB203580, SP600125, ruthenium red). Expression and phosphorylation of MAPKs was investigated using a Western blot.

Results

Hyperthermia induces time- and temperature-dependent cell death in human RPE cells. VEGF expression and secretion is induced by hyperthermia in a time- and temperature-dependent manner mediated by p38 and to a lesser degree by JNK. TRPV channels seem to play a minor role in regulation of hyperthermia-induced VEGF secretion.

Conclusions

Hyperthermia induces temperature-dependent secretion of VEGF in the RPE, which is mediated by p38 and, to a lesser extent, JNK. This may lead to undesired effects from hyperthermal treatment of retinal diseases.     

Cytomegalovirus anterior uveitis: long-term follow-up of immunocompetent patients

Background

We aimed to report on the clinical findings and long-term prognosis of patients with cytomegalovirus (CMV) anterior uveitis.

Methods

This was a retrospective observational study on 15 immunocompetent patients with CMV anterior uveitis and a follow-up longer than 24 months (mean: 62.1?±?28.5 months).

Results

Uveitis was unilateral and hypertensive in all cases, with acute relapsing having the characteristics of Posner-Schlossman syndrome in nine (60 %) and chronic in nine patients (40 %), three of whom were clinically classified as Fuchs’ heterocromic iridocyclitis (20 %). All patients received topical antiviral and corticosteroid therapy, with six patients also receiving systemic therapy with valganciclovir or acyclovir. The mean number of uveitis relapses significantly decreased, before and after anti-CMV therapy, from 0.23?±?0.17 to 0.03?±?0.03 (p?Cataracts developed in nine out of 13 patients (69.2 %). A chronic raise in intraocular pressure (IOP) was found in 13 patients (86.6 %), with nine requiring surgery (60 %). At the end of the follow-up, all patients had a quiescent uveitis, with ten of them requiring topical low dose steroid therapy (66.6 %) and combined with systemic acyclovir in four cases. Eight patients (53.3 %) were on antiglaucomatous therapy. The last mean IOP value was 14.9?±?3.6 mmHg (range 8–21 mmHg), and visual acuity was 0.89?±?0.21.

Conclusions

CMV-associated anterior uveitis has a fairly good long-term visual prognosis. Antiviral therapy can reduce the frequency of relapses, but cataracts and a chronic raise in IOP are frequent complications often requiring a surgical approach.     

Hydrophobic acrylic versus polymethyl methacrylate intraocular lens implantation following cataract surgery in the first year of life

Purpose

To evaluate complication rates following implantation of hydrophobic acrylic versus polymethyl methacrylate (PMMA) intraocular lens (IOL) with cataract surgery in infants.

Methods

Records of children undergoing cataract surgery with IOL implantation in first year of life were retrospectively reviewed. Infants were divided into two groups—hydrophobic acrylic IOLs were implanted in group A, and PMMA IOLs in group B. Outcome measures included incidence of complications, additional surgical procedures, and refractive error changes.

Results

One hundred and thirteen eyes of 113 children (75 males) with mean age of 6.49?±?3.56 months were included. Group A included 62 eyes, and group B included 51 eyes. The two groups did not differ significantly in terms of age and axial length. There was no significant difference between the groups for incidence of posterior capsular opacification (PCO), pupillary membranes, glaucoma, fibrin on IOL surface or IOL malposition (p?=?0.09). Development of PCO was delayed in group A (p?=?0.049). Thirteen eyes of group A and 18 eyes of group B required additional surgical intervention (p?=?0.20) in the follow-up visits.

Conclusion

Comparable complications may be expected in infants with PMMA and hydrophobic acrylic lenses. Children implanted with PMMA IOLs may require earlier surgical re-intervention for PCO.     

Neuronal ceroid lipofuscinosis in The Netherlands-II

This paper is a report on Neuronal Ceroid Lipofuscinosis (NCL) in The Netherlands (synonyms: Batten disease, Jansky-Bielschowsky disease, Batten-Mayou disease, Stock-Spielmeyer-Vogt disease). Discussed are the late infantile type with predominant accumulation of lipofuscin in the form of curvilinear bodies (Jansky-Bielschowsky) and the juvenile type with accumulation of lipofuscin in the form of fingerprint- and rectilinear profiles (Batten-Mayou disease and Stock-Spielmeyer-Vogt disease or F-type of NCL).     

A new model for in vitro testing of vitreous substitute candidates

Purpose

To describe a new model for in vitro assessment of novel vitreous substitute candidates.

Methods

The biological impact of three vitreous substitute candidates was explored in a retinal explant culture model; a polyalkylimide hydrogel (Bio-Alcamid®), a two component hydrogel of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked sodium hyaluronic acid hydrogel (Healaflow®). The gels where applied to explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel-exposed explants were compared with explants incubated under standard tissue culture conditions. Cryosections of the specimens were stained with hematoxylin and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC, Rhodopsin) and TUNEL.

Results

Explants kept under standard conditions as well as PEG-exposed explants displayed disruption of retinal layers with moderate pyknosis of all neurons. They also displayed moderate labeling of apoptotic cells. Bio-Alcamid®-exposed explants displayed severe thinning and disruption of retinal layers with massive cell death. Healaflow®-treated explants displayed normal retinal lamination with significantly better preservation of retinal neurons compared with control specimens, and almost no signs of apoptosis. Retinas exposed to Healaflow® and retinas kept under standard conditions showed variable labeling of GFAP with generally low expression and some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling and Bio-Alcamid®-exposed retinas showed sparse labeling of GFAP.

Conclusions

Research into novel vitreous substitutes has important implications for both medical and surgical vitreoretinal disease. The in vitro model presented here provides a method of biocompatibility testing prior to more costly and cumbersome in vivo experiments. The explant culture system imposes reactions within the retina including disruption of layers, cell death and gliosis, and the progression of these reactions can be used for comparison of vitreous substitute candidates. Bio-Alcamid® had strong adverse effects on the retina which is consistent with results of prior in vivo trials. PEG gel elicits reactions similar to the control retinas whereas Healaflow® shows protection from culture-induced trauma indicating favorable biocompatibility.     

Green tea extract suppresses N-methyl-N-nitrosourea-induced photoreceptor apoptosis in Sprague-Dawley rats

Background

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative human diseases characterized by the loss of photoreceptor cells by apoptosis and eventual blindness. A single intraperitoneal (ip) injection of N-methyl-N-nitrosourea (MNU) causes photoreceptor cell apoptosis within 7 days in rats. Green tea extract (THEA-FLAN 90S; GTE) is a common herbal supplement with pluripotent properties including antioxidant activity. The purpose of the present study was to evaluate the efficacy of GTE against photoreceptor apoptosis in 7-week-old female Sprague-Dawley rats that received a single ip injection of 40 mg/kg MNU.

Methods

The oral administration of 250 mg/kg/day GTE was initiated 3 days prior to MNU injection and continued once daily throughout the experiment. Rats were sacrificed at 12, 24, and 72 h and 7 days after MNU injection, and the eyes were examined morphologically and morphometrically. The photoreceptor cell ratio, retinal damage ratio, and retinal preservation ratio were used to determine the structural and functional alterations. The number of apoptotic photoreceptor cells per mm² was determined in situ by TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL). Our results indicated that oral administration of GTE significantly suppressed the loss of photoreceptor cells morphometrically 7 days after MNU injection. The number of TUNEL-positive cells per mm² in MNU-exposed rat central retina with or without GTE administration was 981 vs. 2056 at 24 h after MNU injection.

Conclusions

GTE structurally and functionally suppressed MNU-induced photoreceptor cell apoptosis. These findings indicate that GTE may help to ameliorate the onset and progression of human RP.     

Factors influencing the exudation recurrence after cataract surgery in patients previously treated with anti-vascular endothelial growth factor for exudative age-related macular degeneration

Purpose

To investigate factors influencing exudation recurrence following cataract surgery in patients already treated with anti-vascular endothelial growth factor (VEGF) agents for exudative age-related macular degeneration (AMD).

Methods

A retrospective review of medical records was performed for patients who underwent cataract surgery and had been previously treated with anti-VEGF for exudative AMD. Visual acuity was examined before surgery and 1 and 6 months after surgery. The time between diagnosis and surgery, and the exudation-free period before surgery were examined and compared between patients who had exudation recurrence and those that did not.

Results

Thirty-nine eyes of 39 patients were included in analyses. The logarithm of the minimum angle of resolution visual acuity was 1.02?±?0.58 and had significantly improved 1 month (0.81?±?0.62, P?P?=?0.001) following surgery. Both the diagnosis-to-surgery period (P?=?0.001) and the preoperative exudation-free period (P?Conclusions Cataract surgery was beneficial in patients previously treated with anti-VEGF for exudative AMD. Our data suggests that cataract surgery should be performed after a sufficiently long exudation-free period to minimize exudation recurrence. But larger prospective studies are required to draw definitive clinical guidelines.     

Effects of adrenergic drugs on aqueous cAMP and cGMP and intraocular pressure

The following variously selective adrenergic agonists were tested for their effects on the concentration of adenosine 3′, 5′ cyclic monophosphate and guanosine 3′, 5′ cyclic monophosphate in the aqueous humor of treated and fellow eyes of rabbits one hour after topical unilateral application (2 mg, base): Epinephrine (α,β₁,β₂), phenylephrine (α), isoproterenol (β₁, β₂), tazolol (β₁) and terbutaline (β₂). All drugs produced a significant increase in cAMP in the treated eyes and all but terbutaline produced a significant increase in the fellow eye. Terbutaline alone caused an increase in cGMP although a similar dose of pilocarpine, a cholinergic agonist, was ineffective in changing cGMP levels. We conclude that (1) diverse adrenoceptor stimulation can increase cAMP, but (2) not necessarily in direct relation to an agent's hypotensive activity and (3) that the hypotension induced by pilocarpine is not accompanied by an increase in aqueous cGMP.     

Changes in the ERG d-wave with vigabatrin treatment in a pediatric cohort

Purpose

Vigabatrin (VGB), a treatment for the childhood epilepsy, infantile spasms (IS), is implicated in visual field constriction. Electroretinograms (ERGs) are used as a substitute for visual field testing in infants. We use the VGB-associated ERG reduction (VAER), defined as reduction in age-corrected light adapted 30 Hz flicker amplitude from a pre-treatment measurement in the absence of other retinal defects, as an indicator of retinal toxicity resulting from VGB use. The d-wave ERG response is predominantly the result of OFF-bipolar cell depolarization response to light offset. The purpose of this study is to evaluate the ERG d-wave response as a marker for VAER toxicity in an infant population.

Methods

One hundred children with IS treated with VGB (median age at baseline: 7.6 months; range 1.7–38.4) were tested for the cone-OFF response elicited to a 250 cd s m² flash with 200 ms duration (long flash ERG). Diagnosis of VAER requires baseline testing of the flicker ERG and at least one follow up ERG; Fifty-one patients fulfilled this criteria. Fifty-eight children received the long flash ERG at baseline. Thirteen retinally normal controls with a median age of 32 months (5.7–65) were also tested. Amplitude and implicit time of the d-wave response were measured manually.

Results

Longer duration of treatment was associated with reduced d-wave amplitude (ANOVA p < 0.05) in patients taking VGB. Nine patients demonstrated VAER during the course of the study. D-wave amplitude was reduced in the IS group with VAER compared to those without VAER (p < 0.05).

Conclusions

Vigabatrin associated retinal defects may be reflected in reduction of the cone d-wave amplitude.     

Measurement of retinal nerve fiber layer and macular ganglion cell–inner plexiform layer with spectral-domain optical coherence tomography in patients with optic nerve head drusen

Purpose

To evaluate the effect of optic nerve head drusen (ONHD) on the retinal nerve fiber layer (RNFL) and macular ganglion cell–inner plexiform layer (GCIPL) using Cirrus optical coherence tomography (OCT).

Methods

Fifty-seven eyes of thirty patients with ONHD and thirty-eight eyes of twenty age-matched and sex-matched control subjects underwent circumpapillary and macular scanning using Cirrus OCT. The percentages of eyes with abnormal GCIPL and RNFL values according to the Cirrus normative data were analysed and compared.

Results

Overall, eyes with ONHD showed abnormally reduced values for average and minimum GCIPL thicknesses in 35 % and 45 % of cases compared to 2 % for both values in control eyes (P?p?=?0.002). The percentage of abnormal thinning increased with higher grades of ONHD for all the parameters evaluated, so that in grade III drusen, values were abnormally reduced in 80 % of eyes in all three analyses. Regarding buried ONHD, 30 % and 4 % of eyes had an abnormally reduced minimum GCIPL and average RNFL thickness, respectively. Furthermore, 26 % of these eyes had abnormal GCIPL exams with a normal or increased RNFL thickness.

Conclusions

Both RNFL and GCIPL analysis reveal significant thinning in eyes with ONHD directly correlated with drusen severity. In buried ONHD, the abnormality rate was significantly higher with GCIPL compared to RNFL evaluation, suggesting that GCIPL analysis might be an early structural indicator of neuronal loss in the setting of thickened RNFL.     

Plasma exchange in the therapy of Behçet's disease

Present therapies for Behçet's disease are unsatisfactory in many cases. We investigated the role of plasma exchange in four patients with severe Beheçet's retinitis who were unresponsive to standard medical therapies. Plasma exchange induced a rapid reduction of ocular inflammation with improved visual acuity in all cases. In patients with severe Behçet's retinitis, plasma exchange is able to interrupt the acute inflammatory activity, but relapses may occur.