Efficacy and Safety of Sarilumab for the Treatment of Posterior Segment Noninfectious Uveitis (SARIL-NIU):: The Phase 2 SATURN Study.

PURPOSE: To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU). DESIGN: Randomized, double-masked, placebo-controlled, phase 2 study. PARTICIPANTS: Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis. METHODS: Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. MAIN OUTCOME MEASURES: The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis. RESULTS: At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 µm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 µm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] µm (P = 0.1317) in the subgroup of eyes with CST ≥300 µm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients). CONCLUSIONS: Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

[The influence of the idiopathic macular hole (IMH) surgery with the ILM peeling and gas tamponade on the electrical function of the retina]. / Vliv operace idiopatické makulární díry s peelingem MLI a plynnou tamponádou na elektrickou funkci sítnice.

Many contemporary clinical papers establish positive influence of the pars plana vitrectomy (PPV) with the ILM (internal limiting membrane) peeling and gas tamponade in macular hole to the macular morphology. They prove diminishing or disappearing of the central scotoma and metamorphopsia and especially also improvement of the BCVA for far and near. The evaluation of the objective functional condition of the retina is still a discussed question. This paper concerns with the comparison of the electric functions of the retina before and after the IMH surgery with the ILM peeling and the gas tamponade. In the group 19 patients (8 men, 11 women), or 19 eyes with IMH were included. The average age was 69 +/- 6 years. The group consisted of patients with transparent optical media. In none of these patients was found other macular pathology than IMH. Nobody underwent other retinal surgery. The patients were examined 1 day before and 1 and 3 months after the surgery. During each control, the following examinations were performed: the Amsler grid examination, the best corrected visual acuity (BCVA) for far (EDRTS chart) and near (Jaeger optotypes), intraocular pressure measurement (non contact tonometer NIDEK NT-2000), examination of the anterior segment on the slit lamp, examination of the posterior segment biomicroscopically and by means of indirect ophthalmoscopy, examination of the photopic, pattern, and multifocal ERG (Retiscan, according to the ISCEV methodology), and OCT examination (Stratus OCT). If necessary, the ultrasound examination (Ultrascan Alcon) was performed as well. For the statistical evaluation of the ERG component values among the data files before the surgery (data file 1), 1 month after the surgery (data file 2), and 3 months after the surgery (data file 3), the non-parametric Wilcoxon pair test was used. In the photopic ERG, there was statistically significant prolongation of the latency b in data file 2 and 3 comparing to the data file 1 (p < 0.05). Comparing latency b of data file 1 to data file 2, there was found no statistical significance. Comparing other parameters of photopic ERG found no statistically significant difference among data files 1,2, and 3. In the multifocal ERG, there was found statistically significant elevation of the P1 amplitude according to the response density of given unit and the P1 amplitude in the central ring in data file 3 comparing to the data file 1 (p < 0.05). Comparison of other parameters was not statistically significant. In the paracentral ring, there was found statistically significant extension of the N1 and P1 latency in data file 3 comparing to the data file 1 (p < 0.05). Comparison of other parameters in the paracentral ring was not statistically significant. Statistically significant improvement of the retinal electric function in the central 4 degrees 3 months after the surgery, confirms the positive functional effect of the surgery to the fovea. In the fovea, the increase of the number of functional nerve cells of the outer layers of the retina occurs. On the other hand, in the parafoveolar region, as well as in the whole retina, 3 months after the surgery, statistically significant decrease of the function of the retina, meaning the time prolongation of the conduction in the outer layers of the retina, occurs. According also to our results, the peeling of the ILM in the IMH surgery remains, despite its unquestionable contribution, still a controversial technique. During the short, three months lasting, follow-up period, the functional improvement in the fovea occurred, but the functional decrease in the parafoveolar region which correlates in the large extent with area of the ILM peeling was found. The discussion about the ILM peeling indication in the earlier stages is adequate. We will further follow-up the development of the retinal electric function after the IMH surgery with ILM peeling and gas tamponade.

[The ERG contribution in early diagnosis of chloroquine and hydroxychloroquine maculopathy]. / Prínos ERG v casné diagnostice chlorochinové a hydroxychlorochinové makulopatie.

Derivates of chloroquine (Plaquenil, Delagil), used for long-term treatment of rheumatic diseases, may cause clinically proven irreversible maculopathy, which may progress even after the discontinuation of their application. The optimal early diagnosis of ocular toxicity of chloroquine or hydroxychloroquine drug remains controversial up to now. The aim of this review paper was to evaluate how appropriate is the indication of the electroretinographic (ERG) examination due to the early diagnosis of cumulative drug-related maculopathy. Photopic, pattern, and multifocal ERG (Retiscan, according to the ISCEV methodology) were examined in 10 patients (20 eyes) treated by means of antimalarics, 9 due to the rheumatoid arthritis (RA) and 1 due to the systemic lupus erythremathodes (SLE). The average age of the patients was 60 +/- 15 years, the treatment period was 10 +/- 11 years; the median of the treatment period was 5 years. The control group consisted of 12 healthy, age matched patients (20 eyes) without any obvious ocular pathology. In all of them, the complete ophthalmologic examination was performed: the best corrected visual acuity (BCVA) for far using the Snellen charts, intraocular pressure (IOP) measured by means of the non contact tonometer NIDEK NT-2000, the Amsler grid test, examination of the anterior segment and the posterior segment with the slit lamp. The entry criteria in both groups were BCVA 5/7,5 (0.67) and better, the IOP in the normal range, negative Amsler grid test, anterior segment without significant decrease of the transparency, and physiological posterior segment or with subtle granular pigment dysgrupancies in the macula only. The significant difference between the group treated with chloroquine or hydrochloroquine and the control group at the 1% level of significance was found in following parameters: in the photopic ERG the value of the b wave latency [ms], in pattern ERG, the values of the waves N35 - P50 [microV] and P50 - N95 [microV] amplitudes, and at the 5 % level of significance in photopic ERG, the wave a amplitude value [microV] and in multifocal ERG, the value of the P1 [ms] a N1 [ms] parts latency in the pericentral ring. It follows from the results, that the ERG examination is suitable for the early diagnosis drug cumulative maculopathy caused by chloroquine derivates. Optimal is the individual comparison of the ERG values of the patient before and in certain time intervals after the beginning of the chloroquine derivates treatment.