PURPOSE:To evaluate the long-term efficacy of and tolerance to adalimumab in patients with juvenile idiopathic arthritis-associated uveitis (JIA-U). METHODS:This retrospective study included patients with JIA-U who completed the ADJUVITE trial with at least 2 years and up to 5 years of follow-up after the end of the trial (i.e. at least 3 years and up to 6 years of follow-up after randomization). Data, including treatment course, visual and anatomical outcomes, uveitis activity evaluated by laser flare photometry, and safety were collected from medical records. RESULTS:Forty-one eyes of 25 participants with a mean age of 10.5 ± 4.0 years at the end of the trial were enrolled. Twenty-one patients (84%) responded to adalimumab during a mean follow-up period of 68.0 ± 21.6 months (range 26-109 months, post-trial), and among the responders, one patient could discontinue adalimumab without further uveitis relapse. Five years after the end of the trial, the mean BCVA improved to 0.07 ± 0.39 logMAR (vs. 0.14 ± 0.20 logMAR, p = 0.048) and the mean anterior chamber flare decreased to 29.9 ± 19.1 ph/ms (vs. 37.2 ± 35.0 ph/ms, p = 0.170). The mean dose of methotrexate decreased significantly from 11.3 ± 4.4 mg/week at the end of the trial to 5.2 ± 6.2 mg/week at the last follow-up (p = 0.002). Four patients did not respond to adalimumab and required other biologics. Adalimumab was well-tolerated in all patients. CONCLUSIONS:Adalimumab was effective in maintaining long-term uveitis control in patients with JIA-U, with a good safety profile. However, complete discontinuation was not possible in most cases, confirming the suspending effect of adalimumab.

A 43-year-old woman with a long history of unilateral optic disc pit maculopathy was referred to our clinic. Twenty years ago, she had presented a first episode of serous macular retinal detachment with favourable initial outcome after laser photocoagulation next to the optic disc pit. Two years ago, 25G vitrectomy with ILM peeling and 16% C2F6 tamponade were performed for massive recurrence of subretinal fluid associated with significant visual loss. Given the lack of results after the first surgery, a second vitrectomy with complementary ILM peeling and new C2F6 tamponade were performed the following year but failed to improve her condition with recurrence of the macular detachment and progressive loss of vision. Upon admission to our clinic, her visual acuity was limited to 20/800 in the pathological left eye. Spectral-domain optical coherence tomography (SD-OCT) revealed a large pit measuring more than 900 μm in horizontal diameter (Fig. 1). The optic disc pit communicated with a wide subretinal fluid cavity that lifted the macula. There was also retinoschisis of the outer retinal layers. Due to the very large size of the pit, we decided to use a silicone lacrimal punctal plug to fill the pit and thus mechanically prevent the penetration of subretinal fluid. We chose the s2-3651 preloaded extra small plug from FCI Ophthalmics® because its dimensions corresponded to the size of the pit (Fig. 2). Under general anaesthesia, standard 3-port 23-gauge pars plana vitrectomy was performed. Brilliant blue injection confirmed that the ILM had previously been peeled all over the macula. The punctal plug was inserted into the vitreous cavity after enlarging superotemporal sclerotomy to 20-gauge sclerotomy. The plug was gently placed into the pit with 23-gauge epiretinal membrane end gripping forceps (Fig. 3 and Video S1). Finally, 20% SF6 tamponade was performed to maintain the plug after fluid-air exchange. No intra- and postoperative complications occurred. After gas resorption, the silicone plug remained stable into the pit (Fig. 4). The OCT scan showed the closure of the connection between the optic disc pit and the subretinal space. Subfoveal fluid was slowly reabsorbed over several months. At 8 months, the anatomical outcome was excellent with a total resolution of serous retinal detachment (Fig. 5). Functionally, visual acuity remained stable at 20/800 probably due to structural alterations of the outer retina previously induced by prolonged serous detachment. Optic disc pit is a rare congenital anomaly resulting from the imperfect closure of the embryonic fissure. Although sometimes asymptomatic, it may cause vision loss when associated with serous macular detachment, a condition referred to as optic disc pit maculopathy. In the absence of treatment, the prognosis of optic disc pit maculopathy is generally poor, leading to visual loss within 6 months of the serous detachment (Sobol et al. 1990). Currently, the treatment of choice for managing optic disc pit maculopathy is pars plana vitrectomy with induction of posterior vitreous detachment, either alone or in combination with other treatment modalities such as internal limiting membrane (ILM) peeling, gas tamponade and laser photocoagulation (Chatziralli et al. 2018). Refractory cases are very challenging, and there is to date no treatment consensus. Recently, several surgical alternatives have been described to seal the optic disc pit, including scleral autograft (Shah et al. 2017), free ILM flap (Hara et al. 2017) and autologous platelet-rich plasma (Todorich et al. 2017). Given the absence of ILM all over the macula, we decided to use a commercially available silicone punctal plug to fill the pit. Silicone punctal plugs are tiny devices normally inserted into tear ducts for temporary occlusion of the lacrimal drainage system in dry eyes. These plugs are sterile, biocompatible, quite cheap and easy to order. Technically, the surgery we described was easier to perform than the ILM flap technique. Although our patient did not have significant visual gain, it is reasonable to assume that a greater benefit could have been observed if the surgery could have been performed earlier. Evidence of the functional efficacy of this technique should be assessed in other patients with less advanced macular involvement, before the onset of definitive internal retinal lesions. Actually, the use of this technique is only possible in large optic disc pit (>500 μm) unless the medical industry develops thinner plugs for this purpose. Regarding the safety of this procedure, other cases are needed to draw conclusions. To evaluate a possible compression of the optic nerve fibres, it would be interesting in future cases to test the visual field before and after surgery. This first case suggests that a silicone punctal plug could be considered an interesting additional option in the surgical treatment of large optic disc pit-associated maculopathy. Further studies are needed to confirm the functional benefit and safety of this technique in larger cohorts. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.