David BenEzra

Cyclosporine Eyedrops for the Treatment of Severe Vernal Keratoconjunctivitis

Twelve children with severe chronic vernal keratoconjunctivitis participated in a pilot study aimed at evaluating the effect of 2% cyclosporine eyedrops on the clinical course and symptoms of this disease. Eleven of the 12 children showed improvement after the first week of treatment. Nine patients demonstrated persistent improvement at the completion of the treatment schedule after six weeks. However, although seven of the children were symptom-free while being treated, only three were free of disease two months after cessation of the cyclosporine eyedrops. The other nine showed rapid recurrence of their symptoms.

Placental growth factor-1 and epithelial haemato–retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy

Aims/hypothesisDisruption of the retinal pigment epithelial (RPE) barrier contributes to sub-retinal fluid and retinal oedema as observed in diabetic retinopathy. High placental growth factor (PLGF) vitreous levels have been found in diabetic patients. This work aimed to elucidate the influence of PLGF-1 on a human RPE cell line (ARPE-19) barrier in vitro and on normal rat eyes in vivo.MethodsARPE-19 permeability was measured using transepithelial resistance and inulin flux under stimulation of PLGF-1, vascular endothelial growth factor (VEGF)-E and VEGF 165. Using RT-PCR, we evaluated the effect of hypoxic conditions or insulin on transepithelial resistance and on PLGF-1 and VEGF receptors. The involvement of mitogen-activated protein kinase (MEK, also known as MAPK)/extracellular signal-regulated kinase (ERK, also known as EPHB2) signalling pathways under PLGF-1 stimulation was evaluated by western blot analysis and specific inhibitors. The effect of PLGF-1 on the external haemato–retinal barrier was evaluated after intravitreous injection of PLGF-1 in the rat eye; evaluation was by semi-thin analysis and zonula occludens-1 immunolocalisation on flat-mounted RPE.ResultsIn vitro, PLGF-1 induced a reversible decrease of transepithelial resistance and enhanced tritiated inulin flux. These effects were specifically abolished by an antisense oligonucleotide directed at VEGF receptor 1. Exposure of ARPE-19 cells to hypoxic conditions or to insulin induced an upregulation of PLGF-1 expression along with increased transcellular permeability. The PLGF-1-induced RPE cell permeability involved the MEK signalling pathway. Injection of PLGF-1 in the rat eye vitreous induced an opening of the RPE tight junctions with subsequent sub-retinal fluid accumulation, retinal oedema and cytoplasm translocation of junction proteins.Conclusions/interpretaionOur results indicate that PLGF-1 may be a potential regulation target for the control of diabetic retinal and macular oedema.

Comparative performance of intraocular lenses in eyes with cataract and uveitis

Purpose: To evaluate the postoperative outcomes in uveitic eyes after phacoemulsification and posterior chamber intraocular lens (IOL) implantation. Setting: Multicenter (19) international study. Methods: This prospective randomized comparative interventional case series comprised 140 eyes of 140 patients who had phacoemulsification and implantation of IOLs of various materials: hydrophobic acrylic (n = 48), silicone (n = 44), poly(methyl methacrylate) (PMMA) (n = 26), or heparin‐surface‐modified PMMA (HSM PMMA) (n = 22). Preoperative and postoperative grading and control of intraocular inflammation were performed. Clinically significant observations, visual outcomes, and the incidence of postoperative complications were recorded. Results: At the final follow‐up, 64 eyes (46.3%) had a best corrected visual acuity of 20/40 or better, an improvement that was highly significant (P < .0001). One day after surgery, the acrylic group had the lowest inflammation values and the silicone group the highest (P = .02). The acrylic group continued to have the lowest inflammation grade values until the 3‐month follow‐up. The acrylic and HSM PMMA groups had the lowest incidence of relapses. Posterior capsule opacification developed in 48 eyes (34.2%), with the highest incidence in the silicone group. Conclusions: Phacoemulsification with IOL implantation in selected uveitic eyes was safe and effective. Acrylic IOLs provided a better visual outcome and lower complication rate than IOLs of other materials.

Cataract surgery in children with chronic uveitis

OBJECTIVE To evaluate the visual outcome of cataract surgery in childrens eyes with chronic uveitis and the feasibility of intraocular lens (IOL) implantation in these cases. DESIGN Retrospective noncomparative case series. PARTICIPANTS Seventeen children (20 eyes) with chronic uveitis, dense cataract, and a preoperative visual acuity of 6/120 or less with follow-up of 5 years after the initial cataract surgery. METHODS In 10 eyes of 10 children (five with juvenile rheumatoid arthritis [JRA] and five with non-JRA-associated uveitis) with uniocular or markedly unequal binocular disease, surgery was carried out through the limbus and a posterior chamber IOL was implanted. In seven children (10 eyes), three with JRA and four with non-JRA-associated disease, a pars plana approach was used, and contact lenses or glasses (for the bilateral cases) were prescribed. RESULTS The postoperative course and immediate restored visual acuities were similar whether an IOL was implanted or not. One month after the surgery, visual acuity improved in all operated eyes. After monocular surgery, in the younger children, contact lenses were poorly tolerated and their use discontinued. These aphakic eyes remained with low vision, developing strabismus on longer follow-up. Children with JRA-associated uveitis were younger, demonstrated an active intraocular inflammation for an extended period after surgery, and tended to have secondary membranes develop, necessitating a second surgical intervention. Five years after the initial surgery, only two of nine eyes (22%) in the JRA group (one aphakic of a bilaterally affected child and one pseudophakic in a child undergoing cataract surgery in one eye) retained a visual acuity of 6/9 and 6/6, respectively. In the other seven eyes, the visual acuity was 6/60 in one pseudophakic eye and 6/240 or less in six eyes (three aphakic and three pseudophakic). In children with non-JRA-associated uveitis, 6 (four aphakic in two patients bilaterally affected and two pseudophakic) of 11 eyes (54.5%) retained a vision of 6/12 or better. CONCLUSIONS Cataract surgery in childrens eyes with uveitis may be beneficial. IOL implantation seems preferable to correction with contact lenses in young children needing surgery in one eye. In children with JRA-associated uveitis, the final visual results remain guarded because of irreversible amblyopia and a more complicated postoperative course. For these cases, a modified management approach and a better surgical technique are needed.

Uveitis in children and adolescents.

Aims: To study the relative occurrence of uveitis (intraocular inflammation) and its causes in children and adolescents. Methods: Patients with uveitis examined and followed during a period of 10 years were categorised by age and sex. All underwent ocular examination and an individually tailored battery of laboratory tests. The intraocular manifestations were classified according to the anatomical location of the inflammation and their most probable cause. The final diagnosis was based on typical clinical ocular and extraocular symptoms and signs and on the results of specific laboratory investigations. Results: Out of 821 patients, 276 (33.1%) were 18 years of age or younger with a male to female ratio of 1 to 1. In these 276 children and adolescents, 70.3% had bilateral ocular involvement. Intermediate uveitis was the most frequent anatomical diagnosis. In many cases, symptoms were mild despite the prominent signs and marked decrease of vision. The underlying cause for the uveitis was evaluated as non-infectious in 184 cases (66.7%) and infectious in 92 cases (33.3%). A potential aetiology and/or a definite clinical diagnosis were established in 74.6% of the cases and only 25.4% of the 276 patients were classified as idiopathic. Juvenile idiopathic arthritis (JIA) was the most common systemic disease association diagnosed in 14.9% of these children. Parasite infestation was the most common infectious association. Conclusions: Uveitis in children and adolescents is not as low as previously reported. Parasite infestation on the one hand and JIA on the other hand are the most common aetiologies associated with the uveitis in these young patients.

Congenital Cataract and Intraocular Lenses

We implanted nine intraocular lenses for the aphakic correction of congenital monocular cataracts in eight children (eight eyes). During follow-up periods ranging from 18 to 50 months in six children, there were no major complications connected to the surgery. Parental cooperation with treatment for amblyopia was satisfactory in all cases. The degree of strabismus, the fixation pattern, and the optokinetic nystagmus responses improved postoperatively in all six. Three children old enough to cooperate during visual testing had visual acuities better than 20/200 and two of these had visual acuities of 20/40. In all six children the sound eye is still patched for three to six hours a day. All six attend regular kindergartens and participate in their normal activities without difficulty.

T-lymphocyte subsets in experimental autoimmune uveitis

The dynamic changes of the lymphocyte subsets in the inflamed ocular tissue in Lewis rats with experimental autoimmune uveitis (EAU) were studied by immunohistopathological evaluation at varying intervals after initiation of the disease. Monoclonal antibodies to specific markers of the rat T-helper/inducer lymphocyte (W3/25) and T-suppressor/cytotoxic lymphocyte (OX-8) were used in the avidin-biotin-peroxidase complex (ABC) method. During the early stages of the disease following the acute inflammatory reaction, the T-helper/inducer lymphocytes are found in larger numbers within the infiltrates, the relative number of the T-suppressor/cytotoxic cells is very low during the initial phases, with a ratio as low as 5 to 1. During the later stages, there is a continuous increase in the relative number of suppressor/cytotoxic cells that reaches the ratio of 1 to 1, or even 1 to 2. It is postulated that the observed changes in the ratios between T-helper/inducer and T-suppressor/cytotoxic cells during the different stages of EAU may reflect the kinetics and regulation of the inflammatory response in autoimmune diseases.

Anti-retinal Auto-antibodies in Vogt-Koyanagi-Harada Syndrome, Behcet's Disease, and Sympathetic Ophthalmia

Sera of patients diagnosed as having the active Vogt-Koyanagi-Harada (VKH) syndrome, Behcets syndrome or sympathetic ophthalmia as well as normal controls were evaluated by ELISA and by staining of normal human retinal tissue using the avidin-biotin-peroxidase complex (ABC) technique for anti-retinal antibodies. No anti-retinal S-antigen antibodies were detected by ELISA. However, autoimmune antibodies were found against the outer segments of photoreceptors and Müller cells in patients with the VKH syndrome, with lower titers in some patients with Behcets syndrome, and in a few patients with sympathetic ophthalmia. These results suggested anti-retinal antibodies were present and that retinal autoimmunity may play a role in pathogenesis in varieties of posterior uveitis. In addition, the indirect immunoperoxidase staining technique may facilitate the diagnosis of VKH in uncertain cases.

Ocular penetration of cyclosporin A. III: The human eye.

The distribution of cyclosporin A (CsA) in the blood, saliva, tears, aqueous humour, vitreous, and cerebrospinal fluid has been studied after oral treatment with 5 mg/kg/day of CsA or application of 2% CsA eye drops in olive oil solution. After oral treatment all patients had high CsA levels in blood. Measurable levels of CsA were also found in the saliva and tears. Patients without any intraocular inflammation or patients with mild uveitis did not have any detectable CsA in the aqueous humour. However, patients with severe uveitis had significant levels of CsA in the aqueous humour and in the vitreous. No CsA was found in the cerebrospinal fluid of two patients with central nervous system manifestations of Behçets disease. After local treatment with 2% CsA eye drops no detectable levels of CsA were found in the blood, the saliva, the aqueous humour, or the vitreous even in patients with severe uveitis.

Traumatic cataract in children: correction of aphakia by contact lens or intraocular lens.

PURPOSE To compare the postoperative complications, visual outcome, and incidence of strabismus in children suffering from traumatic cataract corrected with contact lens or intraocular lens and to follow up the refractive changes in these eyes for an extended period of time. METHODS Forty children, 2 to 13 years old at time of surgery for unilateral traumatic cataract, were followed up for 1.5 to 11 years. Seventeen children were corrected with contact lenses and 23 with intraocular lenses. Thirty-two underwent a primary posterior capsulectomy and anterior vitrectomy. RESULTS The mean follow-up after surgery was 7.4 years for the children with contact lenses and 6.2 years for those with intraocular lenses. The incidence of secondary surgical interventions was higher among the children corrected with contact lenses. The eight children (five with contact lenses, three with intraocular lenses) who did not undergo primary posterior capsulectomy had Nd:YAG capsulectomy within 1 year after surgery. Fifteen of the 23 children with intraocular lenses (65.2%) achieved a best-corrected visual acuity of 20/40, and 17 children (73.9%) had a final visual acuity of 20/50, but only five of 17 children with contact lenses (35.3%) achieved this level of visual acuity. CONCLUSIONS Correction of unilateral aphakia by intraocular lens in children after traumatic cataracts results in better final visual acuities and binocularity with a smaller incidence of strabismus than when correction is carried out by contact lens. Intraocular lens implantation should be considered the primary aphakic correction in children with traumatic cataract.