Bilateral uveitis and macular edema induced by Nivolumab: a case report.

BACKGROUND: Nivolumab is a fully human antibody which is routinely used at first therapy for metastatic melanoma. Usually, side effects are immune-related adverse events. We report a case of a man who developed bilateral anterior uveitis and macular serous retinal detachment during nivolumab treatment for metastatic melanoma. CASE PRESENTATION: A man on nivolumab treatment for a leg melanoma with duodenal and lymph nodes metastases developed a sudden bilateral visual acuity impairment and bilateral non-painfull redness eyes several days after the third infusion. The clinical examination showed a significant decreased of the visual acuity. Slit lamp examination revealed the presence of bilateral granulomatous keratic precipitates, anterior chamber cells +++, bilateral synechiae, bilateral papilledema and macular edema associated with serous retinal detachment in the left eye. The anti-Programmed cells Death-1 was stopped and a topical corticosteroid treatment was administrated. After 8 days of topical corticosteroid treatment visual acuity was worsening with similar optical coherence tomography examination. An oral corticosteroid treatment was started. Evolution was favorable with a decrease of ocular inflammation and a complete visual acuity recovery after 3 weeks. Nivolumab was re-initiated. CONCLUSIONS: This is the second clinical report of bilateral anterior uveitis associated with macular serous retinal detachment related to anti-PD-1 treatment, and the first with nivolumab. Cases of uveitis were reported several times. Although rare, ophthalmologic manifestations that are rapidly recognized and adequately managed can be treated.

Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature.

Verheij syndrome, also called 8q24.3 microdeletion syndrome, is a rare condition characterized by ante- and postnatal growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, developmental delay (DD), cardiac and renal defects and dysmorphic features. Recently, PUF60 (Poly-U Binding Splicing Factor 60 kDa), which encodes a component of the spliceosome, has been discussed as the best candidate gene for the Verheij syndrome phenotype, regarding the cardiac and short stature phenotype. To date, only one patient has been reported with a de novo variant in PUF60 that probably affects function (c.505C>T leading to p.(His169Tyr)) associated with DD, microcephaly, craniofacial and cardiac defects. Additional patients were required to confirm the pathogenesis of this association and further delineate the clinical spectrum. Here we report five patients with de novo heterozygous variants in PUF60 identified using whole exome sequencing. Variants included a splice-site variant (c.24+1G>C), a frameshift variant (p.(Ile136Thrfs*31)), two nonsense variants (p.(Arg448*) and p.(Lys301*)) and a missense change (p.(Val483Ala)). All six patients with a PUF60 variant (the five patients of the present study and the unique reported patient) have the same core facial gestalt as 8q24.3 microdeletions patients, associated with DD. Other findings include feeding difficulties (3/6), cardiac defects (5/6), short stature (5/6), joint laxity and/or dislocation (5/6), vertebral anomalies (3/6), bilateral microphthalmia and irido-retinal coloboma (1/6), bilateral optic nerve hypoplasia (2/6), renal anomalies (2/6) and branchial arch defects (2/6). These results confirm that PUF60 is a major driver for the developmental, craniofacial, skeletal and cardiac phenotypes associated with the 8q24.3 microdeletion.

Long-term outcome after topical ciclosporin in severe dry eye disease with a 10-year follow-up.

AIM: To report a 10-year follow-up of patients suffering from severe dry eye syndrome (DES) initially treated with topical ciclosporin A (tCSA) for 6 months. METHODS: The charts of 26 patients with severe DES related to keratoconjunctivitis sicca (KCS) and followed for a minimum 10-year follow-up were retrospectively reviewed. All of them were treated initially with tCSA for 6 months. The Schirmer I test, fluorescein and lissamine green staining scores and tear film break-up time (TBUT) were recorded to assess clinical symptoms before, during and after treatment. The subjective signs were evaluated with the ocular surface disease index (OSDI) questionnaire. Prolongation and reintroduction of tCSA after the initial treatment and combined treatments were also noted. RESULTS: Overall the median (IQR) duration of tCSA treatment was 23 (7-51) months after a prolonged induction treatment lasting 20 (8-41) months during the 10-year follow-up. For symptoms, a statistically significant difference in the OSDI between baseline and the end of the 10-year follow-up was not found (p=0.67). We noted a statistically significant improvement in all clinical signs after the initial treatment period, still present at the end of follow-up. Only 6.5% of the patients needed reintroduction of tCSA after their prolonged induction treatment. CONCLUSIONS: The improvement observed after an initial tCSA treatment was sustained after a long-term follow-up with few cases requiring additional tCSA treatment. A prolonged induction treatment to decrease initial inflammatory local signs is a promising option in KCS.

Retinal Vein Occlusions: Therapeutic Switch in Macular Oedema Treatment with a 12-Month Follow-Up.

PURPOSE: To compare the visual and anatomical outcomes of patients with macular oedema secondary to retinal vein occlusion (RVO) after a switch from bevacizumab to intravitreal injection of a dexamethasone implant (IVI-DEX) or conversely. METHODS: 48 patients - 40 in the antivascular endothelial growth factor (VEGF) DEX sequence (AD group), 8 in the DEX anti-VEGF sequence (DA group) - were included in this multicentre retrospective study and evaluated at baseline, 1, 3, 6 and 12 months after the switch. The outcome measurements were visual acuity (VA) and central macular thickness (CMT) evaluated by spectral domain optical coherence tomography. Patients were defined as 'good responders' if CMT was ≤ 300 µm after the switch. RESULTS: VA significantly improved at 1 month in the AD group (p = 0.03) but not in the DA group (p = 0.40). CMT decreased significantly in the AD group at 1, 6 and 12 months (p = 0.002, p = 0.005 and p = 0.002, respectively). In the DA group, VA did not change from baseline at any time point, and CMT decreased at 1 month (p = 0.02) but not later on. CONCLUSIONS: In patients with macula oedema secondary to RVO, the switch from bevacizumab to IVI-DEX seems more beneficial in terms of short-term VA and long-term reduction of CMT than the DEX anti-VEGF agent sequence.