CLINICAL FEATURES OF RETINAL METASTASES: New Cases Integrated in a Systematic Review of the Literature.

PURPOSE: To report a cohort of patients diagnosed with retinal metastases (RM), and to integrate these new cases in a systematic review of the literature, analyzing the clinical features and prognosis factors of patients with RM. METHODS: We conducted a retrospective multicenter study including patients with RM. We also performed a full literature review of all published cases with a diagnosis of RM. RESULTS: A total of six new cases were described on multimodal imaging. By combining the data from the literature and from our patients, we report the characteristics of a total of 69 patients. The most frequent primary tumor sites were cutaneous melanoma (36%), lung (23%), gastrointestinal tract (17%), and breast (12%). Multimodal imaging highlighted specific characteristics of RM. Fluorescein and indocyanine green angiography revealed early hypofluorescence followed by progressive filling of intrinsic dilated vessels. Optical coherence tomography demonstrated a hyperreflective intraretinal mass in all cases with or without subretinal fluid, hyperreflective intraretinal dots, or intraretinal fluid. Ultrasonography revealed a medium-high reflective dome-shaped tumor. Fifty-nine percent of the patients died during the follow-up with a mean survival time of 8.8 ± 8.7 months. CONCLUSION: We described here the clinical spectrum of RM and highlighted specific features of the disease.

Aflibercept in real-life for the treatment of age-related macular degeneration using a treat and extend protocol: The Armada study.

PURPOSE: To report the visual and anatomic outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with aflibercept under a standardized Treat and Extend (T&E) protocol for up to 3 years of follow-up in "real-life" practice. METHODS: This retrospective, observational, multicenter study included patients with treatment-naïve nAMD and at least 12 months of follow-up. T&E regimen adjustment was initiated after loading phase. At each visit best-corrected visual acuity (BCVA) and optical coherence tomography parameters were performed. RESULTS: One hundred and thirty-six eyes of 115patients had at least 1 year of follow-up with 114 and 82 eyes completing at least 2 and 3 years of follow-up, respectively (mean follow-up duration: 2.7 ± 1.3 years). Mean age was 78.6 ± 8.6 years old and 52% were women. Mean BCVA increased from 60.6 ± 18.7 letters at diagnosis to 66.9 ± 16.2 letters at 1 year (+6.3 letters, p = 0.003) and remained stable throughout the follow-up period (63.1 ± 20.3 letters (+2.5, p = 0.1) and 64.0 ± 20.1 letters (+3.4, p = 0.27) at 2 and 3 years, respectively). The mean central retinal thickness decreased significantly from 358.2 ± 87.9 µm at baseline to 302 ± 71.7 µm at 12 months and maintained stable after 36 months of follow-up (297.1 ± 76 µm, p < 0.0001). Mean number of injections was 6.6 ± 2.2, 4.8 ± 1.9, and 5.6 ± 1.7 at 1, 2, and 3 years, respectively. Mean cumulative number of 16.4 ± 5.6 injections after 3 years. Mean treatment interval was 6.8 ± 2.5 weeks at 1 year. Eight-week and 12-week treatment interval were achieved in 59.5% and 19.1%, 65.8%, and 36.8% and 69.5% and 41.5% at 1, 2, and 3 years, respectively. CONCLUSIONS: Our study demonstrated that intravitreal injections of aflibercept initiated under a standardized T&E for patients with treatment-naïve nAMD allow for significant visual improvement at 12 months, which was maintained over a 3-year follow-up period.

Costs comparison of treating diabetic macular edema with aflibercept, ranibizumab or dexamethasone at 1 year in France (INVICOST study).

PURPOSE: INVICOST, a medico-economic analysis, compared costs of managing treatment-naive patients with diabetic macular edema (DME) receiving intravitreal injections (IVIs) of aflibercept (AFL), dexamethasone implant (DXI) or ranibizumab (RAN) over 1 year. METHODS: Healthcare resource use and associated costs were estimated using individual patient data from INVICTUS, a prospective, open-label, monocentric study. Healthcare costs comprised direct medical costs such as drug acquisition and administration, consultations and ophthalmological procedures. Costs were assessed from the French National Health Insurance perspective using published national tariffs expressed in 2019 euros. RESULTS: Of the 60 treated eyes, 48 had no treatment switch; 14 received AFL, 19 received DXI and 15 received RAN. AFL-treated eyes received an average of 6.5 IVIs, DXI-treated patients received 2 IVIs and RAN-treated received 6.8 IVIs. All treated eyes received an initial prescription for adjunctive ocular medications and 349 follow-up procedures were performed including an average of 3.9 optical coherence tomography and 3.2 retinography procedures per eye. Average total direct cost of per-eye treatment was €4516 (€1128-€8257). Average cost was €5782 for eyes treated with AFL, €2779 with DXI and €5536 with RAN. Drug therapy was the cost driver: €4394 (76%) for AFL, €1915 for DXI (69%) and €4268 (77%) for RAN. CONCLUSION: The difference in total treatment cost is largely explained by the significantly lower frequency of IVI and annual cost of therapy with DXI, compared with AFL and RAN. INVICOST is the first study comparing treatment costs with AFL, DXI and RAN in France in current clinical practice.

INVICTUS: Intravitreal anti-VEGF and dexamethasone implant comparison for the treatment of diabetic macular edema: A 12 months follow-up study.

PURPOSE: To compare the efficacy of intravitreal injections (IVI) of ranibizumab (Lucentis®, Novartis, Basel, Switzerland; RAN), aflibercept (Eylea®, Bayer, Leverkusen, Germany; AFL) and dexamethasone implant (Ozurdex®, Allergan, Irvine, California; DXI) in the treatment of naive diabetic macular oedema (DME) during a 12-month follow-up, in real life. METHODS: Nineteen eyes treated with RAN, 20 with AFL and 21 with DXI were analysed from inclusion up to 12 months (M12) with intermediate analysis at M6. Best corrected visual acuity (BCVA), fundus and central retinal thickness (CRT) using spectral-domain optical coherence tomography (SD-OCT; Spectralis/HRA, Heidelberg Engineering, Germany) were performed at inclusion, M3, M6 and M12. RESULTS: BCVA improved until 67.9 letters ±13.3 SD (+5.5 letters) at M6 and 69.6 letters ±12 SD (+7.2 letters) at 12 months for RAN group (p = 0.036). For the AFL group it improved until 63.6 letters ±15.2 SD (+6.6 letters) at M6 and 67.5 letters ±12.2 SD (+8.5 letters) at 12 months (p = 0.014). Lastly DXI group improved by 66.9 letters ±15.1 SD (+7.9 letters) at M6 and 68.4 letters ±11.2 SD (+9.4 letters) at 12 months (p = 0.0023). CRT decreased by 124.4 µm at M6 and 99.3 µm at M12 in RAN group, 144.3 µm and 101.5 µm in AFL group and finally 95.6 µm and 162.7 µm in DXI group. CONCLUSION: In summary, these three drugs provide an efficient treatment option with an acceptable benefit-risk ratio for the treatment of naive patients with DME, whether on BCVA or CRT on the first year of treatment.

Pigmented paravenous retinochoroidal atrophy associated with Vogt-Koyanagi-Harada disease: a case report.

BACKGROUND: To describe a unique case of pigmented paravenous retinochoroidal atrophy that developed several years after Vogt-Koyanagi-Harada disease. CASE PRESENTATION: A 28-year-old woman presented with gradual vision loss in both eyes and nyctalopia for 2 years. Past medical history was relevant for Vogt-Koyanagi-Harada disease since the age of 19 and positive HLA-DR4. Funduscopic examination revealed perivascular pigmentary clumping and atrophic changes radiating from the optic disks. Spectral domain optical coherence tomography through the macula demonstrated perifoveal outer retinal layers loss with cystic degeneration. Fundus autofluorescence showed zonal areas of hypoautofluorescence corresponding to the areas of atrophy. Full-field electroretinogram identified mildly reduced scotopic and photopic responses. The patient was diagnosed with pigmented paravenous retinochoroidal atrophy. CONCLUSIONS: Pigmented paravenous retinochoroidal atrophy may be acquired after Vogt-Koyanagi-Harada disease. Pathogenesis of pigmented paravenous retinochoroidal atrophy may involve inflammatory-related precursors on a background of genetic predisposition.

Persistent Placoid Maculopathy: Prognosis Factors and Functional Outcomes.

Purpose: To identify prognosis factors and functional outcomes of persistent placoid maculopathy (PPM). Methods: We collected personal PPM cases and combined them with the data from the literature. Results: 68 eyes of 37 patients with PPM were analyzed, including six new cases. Twenty-six patients were men (70%) with a mean age of 51.8 years old. The mean initial visual acuity (VA) was 0.52 LogMar ± 0.55 for a mean final VA of 0.49 LogMar ± 0.51. Risk factors for poor VA included: initial VA less than 0.2 LogMar (p < .0001), cardiovascular risk factor (p = .008), autoimmune-related and/or systemic pro-inflammatory conditions (p = .003), choroidal neovascularization (p = .001), macular atrophy (p = .03) and absence of systemic corticosteroid treatment (p = .03). Conclusion: PPM is a choroidal inflammation. Identifying prognosis factors may help to guide treatment and follow-up. We showed that anti-inflammatory drugs, and anti-VEGF injections in cases of choroidal neovascularization, may lead to better outcomes.

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study.

AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. RESULTS: In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.

Macular oedema due to immune reconstitution uveitis occurring in an HIV-negative patient without cytomegalovirus retinitis.

We describe a case of immune reconstitution uveitis occurring in an HIV-negative patient with bone-marrow transplant, not directly related to cytomegalovirus retinitis.