Laurent Kodjikian

Biotherapies in inflammatory ocular disorders: Interferons, immunoglobulins, monoclonal antibodies

Biotherapies used in clinical practice for the treatment of ophthalmologic manifestations of systemic diseases include interferons (IFN), intravenous immunoglobulins (IVIG) and monoclonal antibodies (anti-TNF, anakinra, tocilizumab and rituximab). Several open prospective studies have shown the effectiveness of IFN-α (78 to 98% complete remission) for the treatment of severe uveitis in Behcets disease. IFN is capable of inducing prolonged remission and continued after his arrest, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behcets disease. They are almost always (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIG are used for the treatment of Kawasaki disease and Birdshot disease. Several open or retrospective studies showed their effectiveness for the treatment of severe and refractory cicatricial pemphigoid. Tolerance of IVIG is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection associated with this biotherapy limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1R) showed interesting results in terms of efficiency in one small open study in Behcets disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis.

Malignant glaucoma induced by a phakic posterior chamber intraocular lens for myopia

A 23-year-old woman with -14.00 diopters of myopia requested emmetropia for professional reasons. An ICM 130 V2 myopic phakic intraocular lens (IOL) (Staar Surgical AG) was implanted in the posterior chamber. Three days later, the patient developed malignant glaucoma. Pupillary block glaucoma and choroidal hemorrhage or effusion were ruled out. As maximum medical treatment failed, rapid secondary surgery was performed with sclerotomy, aspiration in the midvitreous cavity, and removal of the IOL. The follow-up was 43 months.

Endophthalmitis prophylaxis in cataract surgery: overview of current practice patterns in 9 European countries.

Data on practice patterns for prophylaxis against infectious postoperative endophthalmitis (IPOE) during cataract surgery in 9 European countries were searched in national registers and reviews of published surveys. Summary reports assessed each nations IPOE rates, nonantibiotic prophylactic routines, topical and intracameral antibiotic use, and coherence to the European Society of Cataract & Refractive Surgeons (ESCRS) 2007 guidelines. Although the reliability and completeness of available data vary between countries, the results show that IPOE rates differ significantly. Asepsis routines with povidone-iodine and postoperative topical antibiotics are generally adopted. Use of preoperative and perioperative topical antibiotics as well as intracameral cefuroxime varies widely between and within countries. Five years after publication of the ESCRS guidelines, there is no consensus on intracameral cefuroxime use. Major obstacles include legal barriers or persisting controversy about the scientific rationale for systematic intracameral cefuroxime use in some countries and, until recently, lack of a commercially available preparation.

Reactivation of ocular toxoplasmosis during pregnancy

We wished to assess whether ocular toxoplasmosis can be reactivated during pregnancy in immunocompetent females, and whether such reactivation is confined to the eye or whether the fetus is exposed to the risk of vertical transmission. For this purpose, we retrospectively examined 18 females with ocular toxoplasmosis during the course of 35 pregnancies. Of these 18 patients, seven developed recurrences during seven pregnancies. Due to the potential risk of functional damage to the mother and the possibility of vertical disease transmission to the fetus, we suggest following such cases carefully during pregnancy until the dimensions of the problem are more fully appreciated.

Ocular manifestations in congenital toxoplasmosis

BackgroundRetinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur. The aim of this study was to determine the nature of the latter in treated cases of the disease and to assess their impact on visual function.MethodsFour hundred and thirty consecutive children with serologically confirmed congenital toxoplasmosis were included in this study. Data were prospectively collected using standardized ophthalmological assessment forms. The presence of retinochoroiditis and of associated pathologies was ascertained, and their impact on visual function was assessed.ResultsAfter a median follow-up of 12 years [range 0.6–26 years], 130 children manifested retinochoroiditis. We detected 22 foci of retinochoroiditis at birth and 264 additional ones during the follow-up period. Of these, 48 (17%) were active when first diagnosed. Twenty-five of the 130 children (19%) had other associated ocular pathologies. Of these, 21 (16%) had a strabismus, which was due to macular lesions in 86% of the cases; 7 (5.4%) presented with unilateral microphthalmia, and 4 (3%) with cataracts. Most of these events were detected after the onset of retinochoroiditis. None of the children presented with ocular involvement in the absence of chorioretinal lesions. Macular lesions occurred more frequently in children with associated pathologies (p<0.0001), and associated pathologies were likewise more common in individuals with macular lesions (p=0.0003). Visual impairment occurred in 31/130 cases, and in all but 3 of these eyes it was due not to an associated pathology but to macular retinochoroiditis.ConclusionsAt the end of the follow-up period, ocular involvement existed in 30% of the treated children with congenital toxoplasmosis. Associated eye pathologies were manifested less frequently than anticipated. They may occur later in life and are an indirect marker of the severity of congenital toxoplasmosis, but they do not have a direct impact on visual acuity. The overall functional prognosis of congenital toxoplasmosis is better than would be expected on the basis of literature findings, with only 2 of the 130 children suffering bilateral visual impairment.

Endophthalmitis After Intravitreal Injections: Incidence, Presentation, Management, and Visual Outcome

PURPOSE To report the incidence and characteristics of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents or corticosteroids and to describe the clinical and bacteriologic characteristics, management, and outcome of these eyes with acute endophthalmitis in France. DESIGN Retrospective, nationwide multicenter case series. METHODS From January 2, 2008 to June 30, 2013, a total of 316,576 intravitreal injections from 25 French ophthalmic centers were included. For each center, the number of intravitreal injections was determined using billing codes and the injection protocol was recorded. A registry and hospital records were reviewed to identify patients treated for endophthalmitis after injection during the same time period. The main outcome measures were the incidence of clinical endophthalmitis and visual acuity of endophthalmitis cases. RESULTS During the study period, 65 cases of presumed endophthalmitis were found, giving an overall incidence of 0.021% (2.1 in 10,000 injections) (95% confidence interval [CI], 0.016%-0.026%). The median number of days from injection to presentation was 4 [1-26] days. The most common symptom was vision loss. Bacterial identification was achieved in 43.4%. The most frequent pathogens were gram-positive bacteria (91.3%), including coagulase-negative Staphylococcus in 78.3%. Neither the interval between injection and presentation for endophthalmitis nor the clinical signs differentiated culture-positive from culture-negative cases. In multivariate analysis, the use of a disposable conjunctival mould assist device and the use of prophylaxis with an antibiotic or antiseptic were significantly associated with an increased incidence of endophthalmitis (P = .001). The majority of patients had worse visual acuity after 3 months of follow-up when compared with acuity before endophthalmitis. CONCLUSIONS The incidence of presumed endophthalmitis after intravitreal injections of anti-vascular endothelial growth factors or corticosteroids was low and the prognosis poor. Prevention and management remain challenging. It remains to be determined whether the findings of this study are relevant for other countries using different techniques for intravitreal injections.

Maculopathy in uveitis of juvenile idiopathic arthritis: an optical coherence tomography study

Aim: The aim of this study was to examine the frequency and characteristics of macular lesions observed in juvenile idiopathic arthritis (JIA) uveitis, using optical coherence tomography (OCT). Methods: In this cross-sectional study, 38 consecutive patients were recruited from a tertiary referral center in uveitis. All eyes with JIA uveitis underwent complete ophthalmic examination including OCT 3. Exclusion criterion was the inability to obtain OCT scans. Flare and visual acuity were also analysed by using linear regression. Results: We analysed foveal thickness (FT) and central foveal thickness (CFT), using software mapping, to describe macular lesions in 61 eyes. Maculopathy was observed in 51 eyes (84%) compared with 12% in the literature (p<0.0001) and comprised four types: perifoveolar thickening in 45 eyes (74%), macular oedema in 29 eyes (48%), foveal detachment in 11 eyes (18%) and atrophic changes in six eyes (10%). Only four eyes did not demonstrate any lesion. Conclusions: Among children with JIA uveitis, macular involvement is frequent and characterised by perifoveolar thickening and serous retinal detachment. OCT is a non-invasive instrument. It can easily identify this maculopathy, which could impair visual function, and require therapeutic intensification.

Sarcoidosis and uveitis.

Uveitis is a frequent (20-50%) and early feature of sarcoidosis. Typical sarcoid uveitis presents with mutton-fat keratic precipitates, iris nodules, and anterior and posterior synechiae. Posterior involvement includes vitreitis, vasculitis, and choroidal lesions. Cystoid macular edema is the most important and sight-threatening consequence. Histologic proof from a biopsy is the gold standard for the diagnosis of ocular sarcoidosis. An international workshop has recently established diagnostic criteria for sarcoidosis uveitis when biopsy is unavailable or negative: these are based on a combination of ophthalmological findings and laboratory tests. The value of recent techniques, such as PET-scan and endoscopic ultrasound-guided, fine-needle aspiration of intrathoracic nodes needs to be assessed in future studies. Corticosteroids are the mainstay treatment for sarcoidosis. Systemic corticosteroids are indicated when uveitis does not respond to topical corticosteroids or when there is bilateral posterior involvement, especially macular edema and occlusive vasculitis. In up to 15% of cases, additional immunosuppression is used, including methotrexate, azathioprine, and mycophenolate mofetil. Infliximab and adalimumab have been recently proposed for the treatment of refractory or sight-threatening systemic sarcoidosis.

Fluorodeoxyglucose Positron Emission Tomography for the Diagnosis of Sarcoidosis in Patients with Unexplained Chronic Uveitis

Purpose: To assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with unexplained chronic uveitis. Methods: Retrospective review of 19 18F-FDG PET scans. All patients had normal chest CT. In the final analysis, the authors used criteria similar to the criteria of Abad et al. (Abad S, Meyssonier V, Allali J, et al. Association of peripheral multifocal choroiditis with sarcoidosis: a study of thirty-seven patients. Arthritis Rheum. 2004;51:974–982) for the diagnosis of sarcoidosis-associated uveitis. Results: Ten (53%) whole-body scans were consistent with sarcoidosis. At the end, subsequent mediastinal biopsies proved sarcoidosis in 3 patients; 2 patients were considered as presumed sarcoidosis, and 6 indeterminate sarcoidosis. Conclusion: 18F-FDG PET may show focal uptake suggestive of sarcoidosis in patients with unexplained uveitis.

In-Vitro Study of Bacterial Adherence to Different Types of Intraocular Lenses

ABSTRACT The aim of this study was to determine the adherence of Staphylococcus epidermidis to intraocular lenses made of five different biomaterials: polymethylmethacrylate (PMMA), heparinized PMMA, silicone, hydrophilic acrylic, and hydrogel. The extent of bacterial binding was measured by counting. The results were compared using a one-factor variance analysis. Adherence was weakest on hydrogel and strongest on the silicone polymer. Bacterial adherence to the implant surface must therefore depend on the hydrophobicity or hydrophilicity of the biomaterial.