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Danilo Iannetta,1 Michele De Maria,1 Elena Bolletta,2 Valentina Mastrofilippo,1 Antonio Moramarco,1 Luigi Fontana1 1Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy; 2Ocular Immunology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, ItalyCorrespondence: Danilo IannettaOphthalmology Unit, AUSL-IRCCS Reggio Emilia, Viale Risorgimento 80, Reggio Emilia, ItalyTel +39 0522296520Fax +39 0522295839Email iannettadanilo@gmail.comPurpose: To analyse the efficacy of subretinal injection of recombinant tissue plasminogen activator (rtPA) and gas tamponade for the displacement of submacular haemorrhage (SMH).Methods: This single-centre, retrospective, case series included 25 consecutive patients (25 eyes) who underwent pars plana vitrectomy (PPV) with subretinal rtPA injection and 20% sulphur hexafluoride (SF6) tamponade. The primary outcome was SMH displacement rate, defined as the absence of subretinal blood within (complete) or outside (partial) 1500 μm centred on the fovea one month after PPV. Secondary outcomes were final best-corrected visual acuity (BCVA), central macular thickness (CMT), recurrence probability, number of anti-vascular endothelial growth factor (VEGF) injections after PPV, and intra- and post-operative complications.Results: Successful displacement was obtained in all 25 eyes (100%), with complete and partial displacement obtained in 15 (60%) and 10 (40%), respectively. BCVA significantly improved from 1.81± 0.33 to 1.37± 0.52 LogMar at 12 months from surgery (p = 0.001). The bivariate correlation analysis revealed that earlier the surgery had better visual prognosis at the end of the follow-up (p = 0.007). CMT significantly decreased from 922 ± 273.69 μm at baseline to 403.53 ± 314.64 μm at 12 months follow-up (p < 0.001). SMH recurrence was observed in two (8%) patients with a mean survival time of 11.6 ± 0.339 months and a cumulative survival probability of 88% at the end of follow-up. After PPV, the mean number of anti-VEGF injections was 3.00 ± 0.957 with no correlation with final visual acuity (p = 0.365). No intraoperative complications were recorded. Only one patient developed open funnel retinal detachment 40 days after primary PPV.Conclusion: PPV with rtPA subretinal injection and SF6 tamponade is a safe and effective technique in displacing acute SMHs secondary to neovascular AMD. It is recommended to perform within 14 days from the onset of the symptoms to achieve BCVA improvement at 12 months and proper imaging to plan future anti-VEG treatment.Keywords: macular degeneration, submacular haemorrhage, recombinant tissue plasminogen activator, pars plana vitrectomy, subretinal injection

Anterior uveitis has various causes, but the majority of cases are viral induced. The most common viral anterior uveitis etiology includes double-stranded DNA viruses of the

Coronavirus disease 2019 (COVID-19) vaccines can cause transient local and systemic post-vaccination reactions. The aim of this study was to report uveitis and other ocular complications following COVID-19 vaccination. The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). The cases reported were three herpetic keratitis, two anterior scleritis, five anterior uveitis (AU), three toxoplasma retinochoroiditis, two Vogt-Koyanagi-Harada (VKH) disease reactivations, two pars planitis, two retinal vasculitis, one bilateral panuveitis in new-onset Behçet’s disease, three multiple evanescent white dot syndromes (MEWDS), one acute macular neuroretinopathy (AMN), five retinal vein occlusions (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV) secondary to myopia or uveitis, and one central serous chorioretinopathy (CSCR). Mean time between vaccination and ocular complication onset was 9.4 days (range 1–30 days). Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), 7 after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), 3 after ModernaTX vaccination (mRNA-1273), and 1 after Janssen Johnson & Johnson vaccine (Ad26.COV2). Uveitis and other ocular complications may develop after the administration of COVID-19 vaccine.

Purpose: To evaluate strabismus surgery with intraoperative adjustment of sutures under topical anesthesia in children. Methods: Nineteen children with horizontal deviation underwent a one-stage surgical technique performed under topical anesthesia. Surgery consisted of unilateral or bilateral recession and/or resection of horizontal muscles or the medial or lateral rectus muscles, with intraoperative adjustment of sutures based on alternate prism cover test. Follow-up was done at 1 day and 1, 3, and 6 months postoperatively. Results: Mean age at surgery was 12.68 ± 2.50 years (range: 8 to 16 years). Mean preoperative angle of deviation was 24.21 ± 11.20 prism diopters (PD) (range: −50 to +30 PD) at distance. Mean postoperative angle of deviation at 6 months was 4.11 ± 2.87 PD (range: −10 to +10 PD) at distance. In esotropic patients, the average angle of deviation decreased from +23.80 ± 5.89 PD preoperatively to +4.80 ± 3.35 PD at 6 months, whereas in exotropic patients it decreased from −24.36 ± 12.76 to −3.86 ± 2.77 PD. Seventeen of 19 patients (89%) remained comfortable during surgery, whereas 2 needed an intravenous injection of propofol. The success rate, defined by a postoperative residual angle of deviation of ±8 PD or less, was 89% at 6 months. Conclusions: Strabismus surgery with intraoperative suture adjustment under topical anesthesia in children is a tolerable procedure with encouraging outcomes, representing an alternative to general anesthesia in well-selected children. Clinical evaluation of children and parents is fundamental to predict a likely poor collaboration of the child during surgery, which, if present, would require surgery under general anesthesia. [ J Pediatr Ophthalmol Strabismus . 2019;56(3):173–177.]

The most severe visual impairments due to age-related macular degeneration (AMD) are frequently caused by the occurrence of choroidal neovascularization (CNV). Although photodynamic therapy with verteporfin (PDT-V) is currently a second-line treatment for neovascular AMD, it can be conveniently combined with drugs acting against vascular endothelial growth factor (anti-VEGF) to reduce the healthcare burden associated with the growing necessity of anti-VEGF intravitreal re-injection. Because the common 677 C > T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR-C677T; rs1801133) has been described as predictor of satisfactory short-term responsiveness of AMD-related CNV to PDT-V, we retrospectively examined the outcomes of 371 Caucasian patients treated with standardized, pro-re-nata, photodynamic regimen for 24 months. Responder (R) and non-responder (NR) patients were distinguished on the basis of the total number of scheduled PDT-V (TN-PDT-V) and change of best-corrected visual acuity (∆-BCVA). The risk for both TN-PDT-V and ∆-BCVA to pass from R to NR group was strongly correlated with CT and TT genotypes of MTHFR-C677T variant resulting, respectively, in odd ratios of 0.19 [95% CI, 0.12–0.32] and 0.09 [95% CI, 0.04–0.21] (P

Purpose: New tumor therapies like immune checkpoint inhibitors and small molecule inhibitors of MEK and BRAF have increased the patient's survival rate but can be burdened with severe side-effects including uveitis. Here, we show the spectrum, treatment, and outcome of uveitis types induced by tumor treatment.Methods: In this retrospective study, we have included 54 patients from different centers who were developing uveitis under tumor therapy. A 16-item questionnaire was analyzed for type, treatment, and outcome of uveitis and type of tumor treatment, which we have correlated here.Results: Irrespective of the tumor treatment, most patients developed anterior uveitis. All patients received corticosteroids and some additional immunosuppressive treatments. Cessation of tumor therapy was necessary only in a minority of cases.Conclusions: Ocular autoimmunity should be differentiated from toxic effects of cancer treatment and timely recognized since it can be generally well controlled by anti-inflammatory treatment, preserving the patient's vision without cessation of the tumor treatment.

To evaluate the efficacy of Rituximab (RTX) therapy in patients affected by Vogt-Koyanagi-Harada (VKH) disease poorly controlled by traditional immunosuppressive treatment.Retrospective case series of recurrent VKH uveitis treated with intravenous RTX between January 2019 and November 2020. All patients were treated with intravenous RTX and underwent complete ophthalmic examination, best-corrected visual acuity (BCVA), fundus photography, subfoveal choroidal thickness (SFCT) measurement on enhanced depth imaging optical-coherence tomography (EDI-OCT), fluorescein, and indocyanine green angiography.Five patients were included. All patients received at least 3 RTX infusions. Mean BCVA improved from 20/32 Snellen equivalent at baseline before RTX treatment to 20/28 Snellen equivalent (In these case series, RTX was effective in VHK disease poorly controlled by traditional immunosuppressive treatment.

Summary Vogt–Koyanagi–Harada (VKH) is an autoimmune disease characterized by inflammation in tissues that contain melanocytes. We aimed to increase the knowledge regarding immunological pathways deregulated in VKH disease. We compared the percentages of circulating natural killer (NK), NK T and T cells expressing the activatory markers: CD16, CD69, NK group 2D (NKG2D), natural cytotoxicity triggering receptor 3 (Nkp30), natural cytotoxicity triggering receptor 1 (Nkp46) and the inhibitory marker: NK group 2 member A (NKG2A) in 10 active VKH patients, 20 control subjects (CTR) and seven patients with Behçet disease (BD) by flow cytometry. Cytotoxic potential of NK cells was determined through the degranulation marker CD107a expression after contact with K562 cells by flow cytometry. Moreover, plasmatic levels of 27 cytokines were determined with a multiplex bead-based assay. VKH patients showed higher percentages of NKG2Dpos NK and NK T cells versus CTR. The cytotoxic potential of NK cells induced by K562 cells was comparable between VKH patients and CTR. Finally, higher concentrations of interleukin (IL)-4, IL-5, IL-7, IL-17 and platelet-derived growth factor-subunits B (PDGF-bb) were detected in plasma of VKH patients versus CTR. The immune profile of VKH patients was similar to that of BD patients.

Purpose To evaluate the clinical relevance of subcentimetric lymph node biopsy via mediastinoscopy in patients with presumed ocular sarcoidosis (OS). Methods Retrospective study of consecutive patients who underwent biopsy via mediastinoscopy for suspected OS. The biopsy outcomes and clinical features of patients with subcentimetric nodes and of those with lymph nodes >1 cm were compared. Results A total of 67 patients with presumed OS were included. Forty-two patients (63%) had lymph nodes ≥1 cm in diameter, while 25(37%) showed subcentimetric lymph nodes. Biopsy was consistent with sarcoidosis in 83% of patients with lymph nodes ≥1 cm and in 76% of patients with subcentimetric lymph nodes (p = .60). Patients with OS who had subcentimetric lymph nodes had less lymphopenia (p = .01), lower lysozyme values (p = .03) and a longer diagnostic delay compared to those with larger lymph nodes. Conclusions The biopsy of subcentimetric lymph nodes via mediastinoscopy may provide a histological diagnosis and reduce diagnostic delay.

To report long term results of biologic treatment of severe and refractory Behçet's uveitis (BU) choosing a different biologic agent according to the uveitis clinical features.Retrospective cohort of patients with BU refractory to conventional therapy, who received Interferon (IFN) alpha-2a or Infliximab (IFX) for at least 3 months.Twenty-two patients were included (mean age 29 ± 10 years, 63% males); Fifteen received IFN and 7 IFX, for a mean treatment period of 30 ± 24(SD) months. Twenty (90%) patients discontinued treatment, in most cases for complete remission (77%). Seven patients (32%) showed relapses during treatment and five (23%) after discontinuation. Visual acuity improved significantly in IFN group and all eyes showed a significant decrease in central macular thickness at 12 months.Both IFX and IFN Alpha-2a were effective and well tolerated in the treatment of refractory BU using a customized approach based on the uveitis features.

Purpose: To assess the efficacy of interferon (IFN) alpha-2a in the treatment of post-uveitic refractory macular edema (ME).Methods: Retrospective cohort of patients with post-uveitic refractory ME, who received subcutaneous IFN alpha-2a injections for at least 3 months. Baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) were compared with those at follow-up visits up to 12 months.Results: Thirty-seven patients were included. Treatment duration (median [interquartile range]) was 14[8-24] months with a follow-up of 17[10-38] months. CMT (mean [standard deviation]) decreased from 438[140] to 335[119] μm after 1 month (p < 0.0001) and remained significantly lower up to 12 months (286[98] μm, p = 0.001). BCVA (0.48[0.33] logMAR at baseline) improved by 0.26[0.33] logMAR (p = 0.001) at 12 months. There were 14 recurrences. Seven patients had treatment side effects, without serious adverse events.Conclusions: IFN alpha-2a was effective, safe, and well tolerated in treating post-uveitic refractory ME.

This study compared the outcomes of cataract surgery with intraocular lens (IOL) implantation in patients with juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis treated with antimetabolite drugs and systemic corticosteroids (Non-Biological Group) versus patients treated with antimetabolites and biological drugs (Biological Group). A cohort of patients with cataract in JIA-associated uveitis undergoing phacoemulsification with IOL implantation was retrospectively evaluated. The main outcome was a change in corrected distance visual acuity (CDVA) in the two groups. Ocular and systemic complications were also recorded. The data were collected preoperatively and at 1, 12, and 48 months after surgery. Thirty-two eyes of 24 children were included: 10 eyes in the Non-Biological Group and 22 eyes in the Biological Group. The mean CDVA improved from 1.19 ± 0.72 logMAR preoperatively to 0.98 ± 0.97 logMAR at 48 months (p = 0.45) in the Non-Biological Group and from 1.55 ± 0.91 logMAR preoperatively to 0.57 ± 0.83 logMAR at 48 months (p = 0.001) in the Biological Group. The postoperative complications, including synechiae, cyclitic membrane, IOL explantation, glaucoma, and macular edema, were not statistically different between the two groups. An immunosuppressive treatment with biological drugs can improve the visual outcome after cataract surgery in patients with JIA-associated uveitis, but it does not significantly reduce postoperative ocular complications.

Purpose: To evaluate choroidal structural changes in patients with multiple evanescent white dot syndrome (MEWDS) during the acute and recovery stages.Methods: Enhanced-depth imaging optical cohere...

Retinal vein occlusion (RVO) is the second most common cause of visual loss in the Western World. RVO is usually classified into branch RVO (BRVO) and central RVO (CRVO) according to the anatomical site of the vascular occlusion. The pathogenesis of RVO is not yet fully understood, however an important event is the intraluminal thrombus formation, which is usually secondary to several conditions such as hypertension, hyperlipidemia, diabetes and thrombophilia. The blockage of venous circulation causes an elevation of intraluminal pressure in the capillaries, leading to hemorrhages and leakage of fluid within the retina, increase of interstitial pressure and a consequent reduction of retinal perfusion. Ischemia may develop resulting in secretion of vascular endothelial growth factor (VEGF) that causes further vascular leakage and retinal oedema. VEGF has therefore a leading role in RVO pathogenesis and symptoms. As a consequence use of anti-VEGF agents by intravitreal injections has become very common with the aim to improve the clinical outcomes in these patients. Currently 2 anti-VEGF agents (ranimizumab and aflibercept) have been FDA (Food and Drug Administration) and EMA (European Medicine Agency) approved for the treatment of RVO, while another VEGF inhibitor (bevacizumab) is often used "off-label" in clinical practice. Many treatment regimens have been suggested in the clinical trials with these drugs, as monthly injections or injections when needed, however the ideal regimen has not been defined yet. We conducted a systematic review searching MEDLINE for the following terms: retinal vein occlusion, ranibizumab, bevacizumab, aflibercept, vascular endothelial growth factor, macular oedema. Data were extracted by one author (AG and BE) and checked by a second (BPM, CC). Aim of this article was to review available data for each drug, focusing on their efficacy and safety trying to compare their advantages and limits.