A prospective multicentre randomized placebo-controlled superiority trial in patients with suspected bacterial endophthalmitis after cataract surgery on the adjuvant use of intravitreal dexamethasone to intravitreal antibiotics.

PURPOSE: We aimed to determine whether intravitreal dexamethasone as an adjuvant to intravitreal antibiotics is beneficial in the treatment of suspected bacterial endophthalmitis after cataract surgery. METHODS: Randomized, placebo-controlled superiority trial in three tertiary referral centres in the Netherlands. Patients with suspected bacterial endophthalmitis within 6 weeks after cataract surgery were eligible. A diagnostic vitreous biopsy was taken for culture, and patients received intravitreal injections of 400 µg dexamethasone (without preservatives) or placebo, in addition to 0.2 mg vancomycin and 0.05 mg gentamicin. The vancomycin and dexamethasone or placebo injections were repeated once at day 3 or 4. Primary outcome measure was best-corrected visual acuity (BCVA) at 1 year. RESULTS: Between 1 November 2004 and 1 March 2014 (excluding two interruptions totalling 20 months), 324 eligible patients presented. A total of 167 patients (81 dexamethasone, 86 placebo) were available for the intention-to-treat analysis. Biopsies of 114 patients (68%) were culture-positive. Final BCVA did not differ between the dexamethasone and the placebo group (logMAR 0.31 ± 0.58 versus 0.27 ± 0.50; p = 0.90), nor did the number of patients with final vision of no light perception (LP, 7 versus 13). Pain, corneal oedema, the absence of a red fundus reflex on presentation, LP on presentation and culture of virulent pathogens from biopsy were statistically significantly associated with an unfavourable visual outcome. CONCLUSION: Intravitreal dexamethasone without preservatives as an adjuvant to intravitreal antibiotics does not improve visual acuity (VA) in patients treated for suspected bacterial endophthalmitis after cataract surgery.

Half-dose photodynamic therapy followed by diode micropulse laser therapy as treatment for chronic central serous chorioretinopathy: evaluation of a prospective treatment protocol.

PURPOSE: To evaluate the outcome of a prospective protocol for the treatment of chronic central serous chorioretinopathy (CSC). METHODS: Interventional prospective case series in 59 eyes (59 patients) with active chronic CSC. All patients were first treated with indocyanine green angiography (ICGA)-guided half-dose photodynamic therapy (PDT). In case of persistent serous subretinal fluid (SRF) after a follow-up period of at least 6 weeks, ICGA-guided PDT was repeated. If the SRF persisted after two PDT treatments, additional ICGA-guided high-density subthreshold diode micropulse laser (HSML) therapy was performed. Clinical evaluation included best-corrected visual acuity (BCVA), fundoscopy, OCT, fundus autofluorescence, fluorescein angiography and ICGA. RESULTS: After a single PDT treatment, complete resolution of SRF was seen in 37 of 59 eyes. Of the 22 eyes with no complete resolution of SRF, 19 eyes received a second PDT treatment, after which seven eyes of the 19 eyes showed a complete resolution of SRF. Ten eyes underwent HSML, of which one eye had complete resolution of SRF within 7 weeks. At final follow-up a complete resolution of SRF was present in 80% of all eyes. The mean BCVA improved from 0.28 logMAR at baseline to 0.16 logMAR at final follow-up. Improvement of BCVA was highest after the first treatment (-0.12 logMAR, p < 0.001). CONCLUSIONS: The proposed treatment strategy using half-dose PDT and HSML in active chronic CSC resulted in an anatomical success rate of 80%. The first half-dose PDT treatment has the highest likelihood of a favourable treatment response on OCT and BCVA increase.

Detection of choroid- and retina-antigen reactive CD8(+) and CD4(+) T lymphocytes in the vitreous fluid of patients with birdshot chorioretinopathy.

Birdshot chorioretinopathy (BSCR), a progressive form of non-infectious uveitis, is the strongest HLA-associated disease described to date, with >95% of the patients displaying HLA-A29. Since indirect evidence indicates the involvement of T cells in the etiopathology of the disease, we now isolated, cultured and analyzed the vitreous fluid-infiltrating T cells from two BSCR patients with respect to their phenotype, cytokine profile, clonal distribution and antigen specificity. Phenotypic analyses revealed the predominant presence of both CD4(+) and CD8(+) T cells in vitreous fluid. Further analyses on short term expanded and cloned T cells suggested that eye-infiltrating T cells generally displayed a Th1 like cytokine profile with secretion of high levels of IFN-γ and TNF-α. In one patient an oligoclonal CD4(+) and CD8(+) T cell infiltration, with a moderate to strongly skewed TCR Vß usage was suggestive for an antigen driven infiltration/expansion. Indeed, a number of intraocular CD4(+) and CD8(+) T cells responded to crude retinal and choroidal lysates. These results, which demonstrate for the first time the existence of eye-antigen-specific T cells in the vitreous fluid of BSCR patients, substantiate the current view on the role of eye-antigen specific T cells in the etiopathology of BSCR.

Imaging methods for inflammatory macular edema.

OCT has become the most common way to image ME. It represents morphologic characteristics of ME in detail, allows the quantitative measurements of ME, and depicts the integrity of the photoreceptor layer important for the visual prognosis and further evaluates the otherwise invisible changes of the vitreoretinal interface. Normative data for the different devices are scarce and data from different devices cannot be compared. FA retains its crucial role in determining the activity of the uveitis and also forms an important diagnostic tool. OCT and FA imaging in inflammatory ME are complementary methods, each with its specific indications and outcomes. Ultrahigh-resolution OCT's will bring a further understanding of the pathogenesis of inflammatory ME.

Efficacy of low-dose methotrexate treatment in birdshot chorioretinopathy.

PURPOSE: To ascertain the effect of treatment with methotrexate (MTX) on the visual prognosis of birdshot chorioretinopathy (BSCR). METHODS: Retrospective case series of 76 consecutive patients with HLA-A29-positive BSCR, of whom 46 were followed for at least 5 years and 18 for longer than 10 years. A review of the medical records of 76 patients with BSCR. Treatment regimens were subdivided into the following groups: 1) No systemic immunomodulatory treatment; 2) Treatment with systemic corticosteroids; and 3) Treatments which comprised MTX. First, we calculated eye-years for the different therapeutic regimens and second, we subdivided the patients according to their initial treatment regimen and assessed visual outcomes. RESULTS: Mean visual acuity increased over time in the MTX-treated patients; remained unchanged in patients on systemic corticosteroids and decreased in the patients without systemic treatment (yearly change in LogMar -0.020, -0.034 and 0.028 with P = 0.034, P = 0.71 and P = 0.006 respectively). In the group treated initially with MTX, VA gradually increased in contrast to the remaining groups of patients (P = 0.003). CONCLUSION: In this series, treatment comprising MTX showed better visual outcomes than the untreated patients and corticosteroid-based treatment regimens.

Clinical review: Update on treatment of inflammatory macular edema.

The aim of this review is to summarize the recent developments in the treatment of inflammatory macular edema (ME). Inflammatory ME represents a major cause of visual loss in uveitis and its adequate management is crucial for the maintenance of useful vision in patients with uveitis. Recent studies favor early treatment of inflammatory ME, even in patients with full visual acuity. After recapitulating the standard treatment modalities for inflammatory ME the authors address novel corticosteroid implants. They review the literature on the efficacy of anti-VEGF agents for inflammatory ME and point out their beneficial, but transient effects. Further, they present recent data on the value of systemic biologics in uveitic ME and evaluate the effectiveness of vitrectomy. Finally, they propose an algorithm for the treatment of inflammatory ME and point out that the individual risk-benefit ratio, especially with systemic immunosuppressive therapy, should always be considered.