PACHYCHOROID: an inherited condition?

PURPOSE: Thick choroid (pachychoroid) is associated with central serous chorioretinopathy (CSC), but whether pachychoroid is inherited is unknown. METHODS: In a prospective observational study, first- or second-degree relatives (16 individuals) of 5 patients with CSC had refraction and visual acuity measurement, fundus examination, nonmydriatic photography, and autofluorescence photography. Eyes were graded using the following criteria: 0: normal fundus and autofluorescence photography, 1: focal retinal pigment epithelium hyperfluorescence and/or hypofluorescence and/or retinal pigment epithelial detachment, 2: CSC or diffuse retinal epitheliopathy. Choroid thickness was measured by enhanced depth imaging mode on optical coherence tomography. RESULTS: Considering 395 µm as the threshold limit for normal subfoveal choroidal thickness, 50% of the eyes from relatives had a thick choroid. Nine eyes of Grade 0 (28%) with an isolated pachychoroid would thus have been considered normal, if choroidal thickness was not included as a screening sign predisposing for CSC. CONCLUSION: Our observation suggests that pachychoroid could be an inherited condition with potentially a dominant transmission mode. Its inclusion in the phenotype of CSC for genetic studies should be considered.

SPIRONOLACTONE FOR NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY: A RANDOMIZED CONTROLLED CROSSOVER STUDY.

PURPOSE: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy. METHODS: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity. RESULTS: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0-Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed. CONCLUSION: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo.

Systemic adalimumab induces peripheral corneal infiltrates: a case report.

BACKGROUND: Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab. CASE PRESENTATION: A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks. CONCLUSION: Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy.

Mineralocorticoid receptor antagonism in the treatment of chronic central serous chorioretinopathy: a pilot study.

PURPOSE: Based on experimental data showing that central serous chorioretinopathy could result from overactivation of mineralocorticoid receptor pathway in choroid vessels, the authors studied eplerenone, a mineralocorticoid receptor antagonist, as a potential treatment for chronic central serous chorioretinopathy. METHODS: This nonrandomized pilot study included 13 patients with central serous chorioretinopathy of at least 4-month duration, treated with 25 mg/day of oral eplerenone for a week followed by 50 mg/day for 1 or 3 months. The primary outcome measure was the changes in central macular thickness recorded by optical coherence tomography, and the secondary outcomes included changes in foveal subretinal fluid (SRF) measured by OCT, in best-corrected visual acuity (BCVA) and the percentage of eyes achieving complete resolution of subretinal fluid during the treatment period. RESULTS: Central macular thickness decreased significantly from 352 ± 139 µm at baseline to 246 ± 113 µm and 189 ± 99 µm at 1 and 3 months under eplerenone treatment (P < 0.05 and P < 0.01, respectively). At 3 months, the subretinal fluid significantly decreased compared with baseline subretinal fluid (P < 0.01) and best-corrected visual acuity significantly improved compared with baseline best-corrected visual acuity (P < 0.001). CONCLUSION: Eplerenone treatment was associated with a significant reduction in central macular thickness, subretinal fluid level, and an improvement in visual acuity. Randomized controlled trials are needed to confirm these encouraging results.

Effect of Visual Search Training on Saccades in Age-related Macular Degeneration Subjects.

OBJECTIVE: To compare the impact of unilateral versus bilateral Age-related Macular Degeneration (AMD) on saccadic movements, and to show the effect of visual search training on these eye movement performances in AMD subjects. We hypothesized that unilateral and bilateral AMD subjects had abnormal saccadic performances, and that visual search training could improve their performances. METHODS: Three groups participated in visual search training: 13 elderly unilateral AMD subjects (mean age: 74.6 ± 1.6 years), 15 elderly bilateral AMD subjects (mean age: 74.2 ± 1.2 years), and 15 healthy age-matched control subjects (mean age: 70.9 ± 1.3 years). Horizontal saccadic performances were recorded before and after visual search training (Metrisquare®) with the Mobile Eye Tracker (Mobile EBT®). We analyzed the saccadic movement performances: latency, mean velocity and gain. We measured the training performances for each exercise: the time, the number of omissions and the number of errors. We analyzed the performances with Kruskal-Wallis and posthoc tests. RESULTS: The latency of saccades in AMD subjects is significantly longer compared to healthy elderly for 15° (p<0.03), 10° (p<0.003) and 5° (p<10-3). Unilateral and bilateral AMD subjects normalized their latency of saccades after training for small saccades (respectively p=0.30 and p=0.23 for 10°, and p=0.09 and p=0.52 for 5°). In elderly, performances depend on the saccade's amplitude. CONCLUSION: AMD subjects' saccadic movements are disrupted: the execution needs more time but is efficient. The visual search training improved the saccadic performances in AMD subjects. Further studies will aim to improve knowledge on such issues and to explore the benefit of training over time in unilateral AMD subjects.

Effects of Age-Related Macular Degeneration on Postural Sway.

Purpose: To compare the impact of unilateral vs. bilateral age-related macular degeneration (AMD) on postural sway, and the influence of different visual conditions. The hypothesis of our study was that the impact of AMD will be different between unilateral and bilateral AMD subjects compared to age-matched healthy elderly. Methods: Postural stability was measured with a platform (TechnoConcept®) in 10 elderly unilateral AMD subjects (mean age: 71.1 ± 4.6 years), 10 elderly bilateral AMD subjects (mean age: 70.8 ± 6.1 years), and 10 healthy age-matched control subjects (mean age: 69.8 ± 6.3 years). Four visual conditions were tested: both eyes viewing condition (BEV), dominant eye viewing (DEV), non-dominant eye viewing (NDEV), and eyes closed (EC). We analyzed the surface area, the length, the mean speed, the anteroposterior (AP), and mediolateral (ML) displacement of the center of pressure (CoP). Results: Bilateral AMD subjects had a surface area (p < 0.05) and AP displacement of the CoP (p < 0.01) higher than healthy elderly. Unilateral AMD subjects had more AP displacement of the CoP (p < 0.05) than healthy elderly. Conclusions: We suggest that ADM subjects could have poor postural adaptive mechanisms leading to increase their postural instability. Further studies will aim to improve knowledge on such issue and to develop reeducation techniques in these patients.

Shift Work: A Risk Factor for Central Serous Chorioretinopathy.

PURPOSE: To investigate if shift work or sleep disturbances are risk factors for central serous chorioretinopathy (CSCR). DESIGN: Prospective case-control study. METHODS: Forty patients with active CSCR and 40 controls (age- and sex-matched) were prospectively recruited from the Ophthalmology Department of Hôtel Dieu Hospital, Paris, between November 2013 and December 2014. All patients were asked to complete a questionnaire addressing previously described risk factors and working hours, as well as the Insomnia Severity Index (ISI), a validated instrument for assessing sleep disturbances. RESULTS: The mean age of the CSCR group was 44 ± 9 years, whereas the mean age of the control group was 43 ± 10 years. By use of multivariate analysis, shift work (odds ratio [OR] [95% confidence interval]: 5 [1.2-20.4]; P = .02), steroid use (OR: 5.5 [1.1-26.2]; P = .03), and recent psychological stress (OR: 15.3 [4.1-54.5]; P < .001) were found to be independently associated with CSCR. CONCLUSION: The outcomes of this study suggest that shift work is an independent risk factor of CSCR. Further studies are required to confirm these results and to examine if work reconversion would be beneficial in the treatment of patients with chronic/recurrent CSCR.

Subconjunctival injection of XG-102, a JNK inhibitor peptide, in patients with intraocular inflammation: a safety and tolerability study.

PURPOSE: We aimed to investigate the safety, tolerability, and systemic diffusion of a single escalating dose of XG-102 (a 31-D-amino-acid peptide inhibiting JNK pathway activation), administered subconjunctivally in the treatment of post-surgery or post-trauma intraocular inflammation. METHODS: This is a dose-escalating, tolerance Phase Ib study. Twenty patients with post-surgery or post-traumatic intraocular inflammation were assigned to 1 of the 4 dose escalating (45, 90, 450, or 900 µg XG-102) groups of 5 patients each. Patients were evaluated at 24, 48 h, 8, and 28 days following the administration of XG-102, including laboratory tests, standard eye examinations, vital signs, and occurrence of adverse events. A single plasma quantification of XG-102 was performed 30 min after administration, according to previous pharmacokinetics studies performed on volunteers. RESULTS: A total of 17 non-serious adverse events, considered unrelated to the study treatment, were reported for 10 patients. The adverse event incidence was not related to the drug dose. All patients experienced a decrease in intraocular inflammation as of 24 h post-administration and this decrease was sustained up to 28 days thereafter. No patient required local injection or systemic administration of corticoids following the administration of XG-102. XG-102 was undetectable in the first 3 dose groups. In the fourth-dose group (900 µg) the XG-102 plasma levels were above the limit of detection for 3 patients and above the limit of quantification for 1 patient. CONCLUSIONS: In this first clinical trial using XG-102, administered as a single subconjunctival injection as adjunct therapy, in patients with recent post-surgery or post-trauma intraocular inflammation is safe and well tolerated. Further studies are required to evaluate its efficacy.

Resolution of foveal detachment in dome-shaped macula after treatment by spironolactone: report of two cases and mini-review of the literature.

Dome-shaped macula (DSM) was recently described in myopic patients as a convex protrusion of the macula within a posterior pole staphyloma. The pathogenesis of DSM and the development of associated serous foveal detachment (SFD) remain unclear. The obstruction of choroidal outflow and compressive changes of choroidal capillaries have been proposed as causative factors. In this paper, we report two cases of patients with chronic SFD associated with DSM treated with oral spironolactone. After treatment, there was a complete resolution of SFD in both patients. To the best of our knowledge, this is the first report of successful treatment of SFD in DSM by a mineralocorticoid receptor antagonist.