Switching to subtenon triamcinolone acetonide does not jeopardize the functional and anatomic outcomes of dexamethasone implant treated eyes with diabetic macular edema.

BACKGROUND: Intraocular dexamethasone implant (DEXi) is an efficient treatment for diabetic macular edema (DME). However, it may be unavailable or contraindicated. Triamcinolone acetonide is another corticosteroid that has proved to be safe and effective in treating macular edema complicating various diseases including diabetes. The purpose of this study is to evaluate the outcomes of a switch from DEXi to subtenon triamcinolone acetonide (STTA) and back, in eyes with DME. METHODS: Retrospective study. DME eyes that had been treated with DEXi and switched to STTA between October 2018 and February 2019 (stock shortage of DEXi) were included. The functional and anatomical outcomes of the switch and switch-back were studied. RESULTS: 26 eyes of 17 patients (mean age 67.1 ± 8.2 years) were considered. The mean baseline visual acuity (VA) was 0.35 ± 0.17 decimals remaining stable after DEXi, STTA and switch-back to DEXi. The mean central macular thickness (CMT) was 492.7 ± 32.8 µm initially, decreasing to 294.3 ± 133.4 µm after DEXi, 369.9 ± 182.3 µm after STTA and 297.6 ± 72.0 µm after switching back to DEXi (all p < 0.05 versus baseline). Compared to baseline, the CMT reduction was numerically better after DEXi and switching back to DEXi than after STTA (mean reduction: -200.4 µm, -167.7 µm, and -95.08 µm respectively, p = 0.13). Intraocular pressure was comparable after DEXi and STTA. CONCLUSION: DEXi is the steroid of choice in DME. However, STTA can be a cost-effective alternative when DEXi is unavailable or contraindicated. This study suggests that STTA may be used in the context of a step therapy in DME.

Efficacity and Safety of the Fluocinolone Acetonide Implant in Uveitic Macular Edema: A Real-Life Study from the French Uveitis Network.

PURPOSE: To evaluate the safety and efficacy of the fluocinolone acetonide implant (FAi, Iluvien® Horus pharma, Nice, France) in non-infectious uveitic macular edema (UME) and to approach the predictive factors of treatment response. METHODS: This retrospective, multicenter real-life study included patients with chronic non-infectious UME who received intravitreal FAi after at least two dexamethasone implants (DEXi). RESULTS: Twenty-six eyes from 22 patients (73.1% of females) were included. The mean age was 60.4 ± 16 years. The mean follow-up was 11.4 ± 2 months. The mean baseline best-corrected visual acuity (BCVA) was 0.43 ± 0.36 LogMAR, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). The mean baseline central macular thickness (CMT) was 429 ± 110 µm, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). Five eyes (19.2%) developed ocular hypertension during the follow-up, requiring initiation or strengthening of intraocular pressure lowering medication. The majority of eyes (77%) did not require any rescue DEXi during the available 12-month follow-up. The resolution of UME after DEXi seemed to predict the anatomical response after FAi. The baseline presence of a disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HRF) were both associated with a higher likelihood of requiring rescue DEXi injections. CONCLUSION: FAi implantation led to a significant BCVA and CMT improvement with a good safety profile over the 12-month follow-up. Predictive factors of treatment outcomes seem to include the anatomical response to DEXi and the presence of DRIL and HRF at baseline.

Automated detection of vitritis using ultrawide-field fundus photographs and deep learning.

PURPOSE: Evaluate the performance of a deep learning (DL) algorithm for the automated detection and grading of vitritis on ultra-wide field (UWF) imaging. DESIGN: Cross-sectional non-interventional study. METHOD: UWF fundus retinophotographs of uveitis patients were used. Vitreous haze was defined according to the 6 steps of the SUN classification. The DL framework TensorFlow and the DenseNet121 convolutional neural network were used to perform the classification task. The best fitted model was tested in a validation study. RESULTS: 1181 images were included. The performance of the model for the detection of vitritis was good with a sensitivity of 91%, a specificity of 89%, an accuracy of 0.90 and an area under the ROC curve of 0.97. When used on an external set of images, the accuracy for the detection of vitritis was 0.78. The accuracy to classify vitritis in one of the 6 SUN grades was limited (0.61), but improved to 0.75 when the grades were grouped in three categories. When accepting an error of one grade, the accuracy for the 6-class classification increased to 0.90, suggesting the need for a larger sample to improve the model performances. CONCLUSION: We describe a new DL model based on UWF fundus imaging that produces an efficient tool for the detection of vitritis. The performance of the model for the grading into 3 categories of increasing vitritis severity was acceptable. The performance for the 6-class grading of vitritis was limited but can probably be improved with a larger set of images.

Cerebro-Ocular Toxocariasis Revealed by Bilateral Cystoid Macular Edema.

DESIGN: Case Report Case description: This report describes the case of a female patient diagnosed with oculo-cerebral toxocariasis manifesting initially in the form of isolated bilateral cystoid macular edema. Diagnosis was made by means of positive anterior chamber and lumbar puncture western blots. The unusual presentation, ancillary findings and treatment are discussed. The control of intraocular inflammation that was only partially responsive to steroids was eventually achieved with pegylated interferon alfa-2a. CONCLUSION: Isolated macular edema is a rare presentation of ocular toxocariasis. Interferon alfa-2a may prove useful in case of insufficient control of inflammation.

Atypical retinopathy in ataxia with vitamin E deficiency: report of a sibship.

Typical retinitis pigmentosa (RP) may not be the only retinal phenotype encountered in ataxia with vitamin E deficiency (AVED). The following short case series describes a novel form of retinopathy in AVED. We describe two patients with AVED belonging to the same consanguineous sibship. Both presented an unusual retinopathy consisting of scattered, multifocal, nummular, hyperautofluorescent atrophic retinal patches. The retinopathy remained stable under vitamin E supplementation. We hypothesize these changes to be the result of arrested AVED-related RP following early supplementation with α-tocopherol acetate.

Pan fibroblast growth factor receptor inhibitor associated retinopathy.

PURPOSE: To report a case of Fibroblast Growth Factor Receptor inhibitor (FGFRi) associated retinopathy in a patient treated with Erdafitinib. CASE REPORT: A patient with a history of non-muscle invasive urothelial carcinoma treated with Erdafitinib developed symptomatic unifocal bilateral serous retinal detachments (SRD) eight weeks after starting this new treatment. Six months after discontinuing the drug, the SRDs resolved and visual acuity recovered to baseline. However, hyper and hypo auto fluorescent lesions were still visible on fundus autofluorescence, suggesting a still ongoing retinal pigment epithelium (RPE) impairment. CONCLUSIONS: Cancer treatments using FGFRi are showing promising results but their ocular toxicity is not well reported nor fully understood. Oncologists should be aware of the potential risks associated with FGFRi and involve ophthalmologists for the follow-up of their patients. The toxicity of FGFRi seems to resolve after drug continuation, but a certain degree of infra clinical RPE impairment may persist. Longer term follow-ups are warranted to further understand the effects of FGFRi on the RPE.

Choroidal Nodules in Ocular Sarcoidosis.

BACKGROUND AND AIM: Ocular sarcoidosis is present in 30-60% of all sarcoidosis patients. Our purpose is to increase awareness of the various presentations of ocular sarcoidosis. METHODS: Short image-based clinical case report. RESULTS: We report on a case of ocular sarcoidosis presenting with unilateral choroidal nodules in a middle-aged man. Sarcoid uveitis is generally bilateral and rather symmetrical. However, choroidal nodules are an exception to this rule, as they generally arise unilaterally. Choroidal nodules are highly responsive to oral corticosteroids. When left untreated, they may evolve to chorioretinal atrophy and secondary choroidal neovascularization. CONCLUSIONS: Knowledge of this presentation of ocular sarcoidosis can help clinicians optimize treatment outcomes for patients.

Ocular Toxocariasis in Adult Caucasian Patients: Clinical Presentations and Treatment Outcomes.

PURPOSE: To report the clinical features and treatment outcomes in adult Caucasians with ocular toxocariasis (OT) and investigate their prognosis depending on their serological status. METHODS: Retrospective observational cohort study (2016-2021) including consecutive adults with uveitis and positive western blot (WB) in the aqueous humor or vitreous. The presence of serum antibodies was not necessary for inclusion, allowing to compare the outcomes depending on the serological status. RESULTS: Seventeen eyes of 15 patients were included. Mean age at diagnosis was 51.9 years. Vitreous inflammation was the most frequent sign (100%). Vitreoretinal tractions (41.2%) and chorioretinal granulomas (58.8%) were less prevalent. Atypical features were: spontaneous intravitreal hemorrhage (23.5%), exudative retinal detachment (11.8%), isolated macular edema (17.6%), papillitis (29.4%) and vasculitis (47.1%). Twenty percent of patients had a positive serum serology. Baseline clinical features did not differ statistically depending on the serological status; however, the degree of inflammation was numerically higher in patients with negative serology. Overall, macular thickness, anterior and posterior segment inflammation improved significantly after treatment with oral albendazole, systemic ± local corticosteroids. Vitrectomy (47.1%) was performed in case of persistent vitritis (62.5%), retinal detachment (12.5%) and intravitreous hemorrhage (25%). CONCLUSION: OT has no pathognomonic sign and atypical presentations were not infrequent in this adult Caucasian cohort. Serum antibodies were rarely positive, stressing on the importance of ocular sample analysis, especially in case of atypical features. Serum antibodies may prove useful in forecasting the rapidity of inflammation clearance. Antiparasitic and anti-inflammatory treatment was safe and efficient in most cases.

Efficacy and Safety of Low-Intensity Pulsed Ultrasound-Induced Blood-Retinal Barrier Opening in Mice.

Systemic drugs can treat various retinal pathologies such as retinal cancers; however, their ocular diffusion may be limited by the blood-retina barrier (BRB). Sonication corresponds to the use of ultrasound (US) to increase the permeability of cell barriers including in the BRB. The objective was to study the efficacy and safety of sonication using microbubble-assisted low-intensity pulsed US in inducing a transient opening of the BRB. The eyes of C57/BL6J mice were sonicated at different acoustic pressures (0.10 to 0.50 MPa). Efficacy analyses consisted of fluorescein angiography (FA) performed at different timepoints and the size of the leaked molecules was assessed using FITC-marked dextrans. Tolerance was assessed by fundus photographs, optical coherence tomography, immunohistochemistry, RT-qPCR, and electroretinograms. Sonication at 0.15 MPa was the most suitable pressure for transient BRB permeabilization without altering the morphology or function of the retina. It did not increase the expression of inflammation or apoptosis markers in the retina, retinal pigment epithelium, or choroid. The dextran assay suggested that drugs up to 150 kDa in size can cross the BRB. Microbubble-assisted sonication at an optimized acoustic pressure of 0.15 MPa provides a non-invasive method to transiently open the BRB, increasing the retinal diffusion of systemic drugs without inducing any noticeable side-effect.

Anterior Chamber Cytology Confirms the Diagnosis of T-cell Prolymphocytic Leukemia Masquerading as Viral Retinal Necrosis.

PURPOSE: To describe a case of T-cell prolymphocytic leukemia (T-PLL) masquerading as viral retinal necrosis (VRN). CASE PRESENTATION: A 75-year-old-man with a history of T-PLL in complete remission complained of an acute vision loss in his right and only eye. Ophthalmic examination demonstrated the presence of anterior chamber cells, mild vitritis, and peripheral retinal whitening with intraretinal hemorrhages evocative of VRN. While the anterior chamber tap came back negative for HSV, VZV, and CMV, cytology performed on the aqueous humor described the presence of leukemic cells. CONCLUSION: T-PLL can rarely masquerade as a viral retinal necrosis. Diagnostic work-up should therefore always rule out the infectious causes of retinitis. Anterior chamber tap can sometimes prove useful in the diagnosis of T-PLL even in the absence of a hypopyon, avoiding the need for vitrectomy.

Clinical and Virological Characteristics and Prognostic Factors in Viral Necrotizing Retinitis.

Purpose: Describe the clinical and virological characteristics of viral necrotizing retinitis (VNR) and assess its prognostic factors. Methods: Retrospective study (Pitié Salpêtrière Hospital, Paris) of consecutive VNR patients diagnosed and monitored by qPCR on aqueous humor between 2015 and 2019. All patients received induction therapy with intravenous +/− intravitreal injections (IVI) of antivirals. Results: Forty-one eyes of 37 patients with a mean age of 56 years were included. Involved viruses were VZV (44%), CMV (37%) and HSV2 (19%). Acute retinal necrosis represented 51%, progressive outer retinal necrosis 12% and CMV retinitis 37% of eyes. Forty-six percent of patients were immunocompromised. Median BCVA was 0.7 LogMAR at baseline and 0.8 LogMAR after an average of 14.1 months. VNR bilateralized in 27% of cases after 32 months. Retinal detachment (RD) occurred in 27% of cases after a mean duration of 98 days. Factors associated with a "poor BCVA" at 1 month were: advanced age, low baseline BCVA, high vitritis grade and viral load (VL) at baseline and the "slow responder" status (i.e., VL decrease <50% after 2 weeks of treatment). Factors associated with RD were: advanced age, immunocompetence, low baseline BCVA, high vitritis grade at baseline and use of ≤5 IVIs. Conclusions: Clinical factors including advanced age, immunocompetence, low BCVA and high vitritis grade at baseline were associated with a poor prognosis. New virological factors were predictive of a poor outcome: high baseline VL and the "slow responder" status. Sequential intraocular fluid sampling might help prognosticate the outcomes of VNR.

Ocular Inflammation Induced by Immune Checkpoint Inhibitors.

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients (36 ocular IRAEs), occurring after an average of 17 weeks (±19). Forty-six percent of patients were treated for metastatic melanoma. Anti-PD1 agents were responsible for 57% of the IRAEs. Anterior uveitis was the most common (44%), followed by panuveitis (28%). Of 25 uveitis cases, 80% were bilateral and 60% were granulomatous. We found one case with complete Vogt-Koyanagi-Harada syndrome and one case of birdshot retinochoroidopathy. The other IRAEs were eight ocular surface disorders, one optic neuropathy, and one inflammatory orbitopathy. Seventy percent of the IRAEs were grade 3 according to the common terminology of AEs. ICPIs were discontinued in 60% of patients and 50% received local corticosteroids alone. The literature review included 230 uveitis cases, of which 7% were granulomatous. The distributions of ICPIs, cancer, and type of uveitis were similar to our cohort. Ocular IRAEs appeared to be easily controlled by local or systemic corticosteroids and did not require routine discontinuation of ICPIs. Further work is still warranted to define the optimal management of ocular IRAEs.

Lower Relapses Rate With Infliximab Versus Adalimumab in Sight-Threatening Uveitis: A Multicenter Study of 330 Patients.

PURPOSE: To compare the relapse rate of sight-threatening noninfectious uveitis (NIU) in patients treated with infliximab (IFX) or adalimumab (ADA). DESIGN: Observational retrospective multicenter study. METHODS: A total of 330 patients (median age, 36 years; interquartile range, 27-54), 45.2% men) with sight-threatening NIU (ie, retinal vasculitis and/or macular edema) treated with anti-tumor necrosis factor [TNF]-α agents (IFX intravenously at 5 mg/kg at weeks 0, 2, 6, and every 4 to 6 weeks or ADA subcutaneously at 80 mg, then 40 mg every 2 weeks). Data were obtained retrospectively from patients' medical records. Main outcome measures were relapse rate, complete response of NIU, corticosteroid sparing effect, and safety. RESULTS: Main etiologies of uveitis included Behçet disease (27%), idiopathic juvenile arthritis (5.8%), and sarcoidosis (5.5%). The estimated relapse rate at 6 months after introduction of biological agents was 13% (95% CI = 0.009-0.16). IFX was associated with less relapse risk than ADA (hazard ratio [HR] = 0.52, 95% CI = 0.36- 0.77, P = .001). ADA and IFX were comparable in terms of complete response rate of NIU as well as corticosteroid-sparing effect. Behçet disease was associated with higher odds of complete response (HR = 2.04, 95% CI = 1.16 -3.60, P = .01] and lower relapse rate (HR = 0.53, 95% CI = 0.33-0.85, P = .009) than other causes of NIU with anti-TNF-α agents. CONCLUSIONS: In sight-threatening NIU, IFX seems to be associated with a lower relapse rate than ADA.

Hypoxia Inhibits Subretinal Inflammation Resolution Thrombospondin-1 Dependently.

Hypoxia is potentially one of the essential triggers in the pathogenesis of wet age-related macular degeneration (wetAMD), characterized by choroidal neovascularization (CNV) which is driven by the accumulation of subretinal mononuclear phagocytes (MP) that include monocyte-derived cells. Here we show that systemic hypoxia (10% O2) increased subretinal MP infiltration and inhibited inflammation resolution after laser-induced subretinal injury in vivo. Accordingly, hypoxic (2% O2) human monocytes (Mo) resisted elimination by RPE cells in co-culture. In Mos from hypoxic mice, Thrombospondin 1 mRNA (Thbs1) was most downregulated compared to normoxic animals and hypoxia repressed Thbs-1 expression in human monocytes in vitro. Hypoxic ambient air inhibited MP clearance during the resolution phase of laser-injury in wildtype animals, but had no effect on the exaggerated subretinal MP infiltration observed in normoxic Thbs1-/--mice. Recombinant Thrombospondin 1 protein (TSP-1) completely reversed the pathogenic effect of hypoxia in Thbs1-/--mice, and accelerated inflammation resolution and inhibited CNV in wildtype mice. Together, our results demonstrate that systemic hypoxia disturbs TSP-1-dependent subretinal immune suppression and promotes pathogenic subretinal inflammation and can be therapeutically countered by local recombinant TSP-1.

Epiretinal Membrane Peeling in Eyes with Retinal Vein Occlusion: Visual and Morphologic Outcomes.

INTRODUCTION: To evaluate the anatomical and functional outcomes of pars plana vitrectomy (PPV) and epiretinal membrane (ERM) peeling in patients with retinal vein occlusion (RVO) and secondary ERM. METHODS: Retrospective, multicenter study including patients with RVO and ERM who underwent PPV and ERM peeling with or without phacoemulsification. Demographic, clinical, surgical, and optical coherence tomography (OCT) features were recorded at the time of ERM peeling (baseline). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were longitudinally collected up to 36 months after surgery. Clinical factors associated with BCVA and CMT and disappearance of macular edema during follow-up were investigated. RESULTS: Twenty-one eyes of 21 patients with a median follow-up of 18 months were included. The BCVA improved significantly after ERM peeling (baseline vs. 24 months, p = 0.01). Absence of the external liming membrane/ellipsoid zone on OCT was associated with worse visual outcomes (regression estimate [95% confidence interval, CI] = 0.93 [0.39-1.48] logMAR, p = 0.004). Eyes with disorganization of the inner retinal layers at baseline had higher CMT values at each visit (regression estimate [95% CI] = 114.1 [78.9-219.4] µm, p = 0.004). Older age at the time of RVO (p = 0.03) and branch RVO (p = 0.04) were risk factors for persistent macular edema after ERM removal. CONCLUSION: PPV and ERM removal provided encouraging functional and morphological results in eyes with RVO, with disappearance of macular edema in most eyes. The integrity of the outer retina and preservation of inner retinal segmentation were associated with better visual and anatomical outcomes after ERM removal, respectively.

Intravitreal Dexamethasone in Diabetic Macular Oedema: A Way of Enhancing the Response to Anti-VEGF in Non- or Poor Responders?

BACKGROUND AND PURPOSE: The aim of this study was to describe the outcomes of a switch back to anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DME) eyes treated temporarily with a dexamethasone implant (DEXi), after an initial poor response to anti-VEGF. METHODS: The study involved a case series. RESULTS: Twenty-three eyes of 17 patients were included. All were poorly responsive to anti-VEGF and switched to a DEXi after a mean of 12 anti-VEGF injections. The mean best-corrected visual acuity (BCVA) increased from 0.25 ± 0.19 (decimals) to 0.29 ± 0.20 after switching to the DEXi (p = 0.11). BCVA remained stable (0.31 ± 0.23; p = 0.11) after switching back to anti-VEGF, one month after the last injection. The mean central macular thickness (CMT) decreased significantly from 517.0 ± 128.5 µm to 343.4 ± 118.9 µm (p < 0.001) after switching to the DEXi. In eyes receiving ≥3 anti-VEGF injections during the switch back, the CMT 1 month after the last anti-VEGF injection was significantly decreased compared to the CMT before the switch to the DEXi (mean change of - 95.55 ± 89.82 µm, p = 0.005). CONCLUSION: Switching back poorly responsive DME eyes to anti-VEGF after temporary DEXi therapy is associated with good anatomical and visual outcomes similar to those obtained with the DEXi, provided that at least 3 anti-VEGF injections are administered. The DEXi might restore retinal sensitivity to anti-VEGF.

Disentangling the association between retinal non-perfusion and anti-VEGF agents in diabetic retinopathy.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM) and the leading cause of blindness in patients with DM. In the pathogenesis of DR, chronic hyperglycemia leads to biochemical and structural alterations in retinal blood vessels' wall, resulting in hyperpermeability and non-perfusion. Since vascular endothelial growth factor (VEGF) has been found to play a significant role in the pathogenesis of DR, this review sheds light on the effect of intravitreal anti-VEGF agents on retinal non-perfusion in patients with DR. Based on the existing literature, anti-VEGF agents have been shown to improve DR severity, although they cannot reverse retinal ischemia. The results of the published studies are controversial and differ based on the location of retinal non-perfusion, as well as the imaging modality used to assess retinal non-perfusion. In cases of macular non-perfusion, most of studies showed no change in both fundus fluorescein angiography (FFA) and optical coherence tomography (OCTA) in patients with DR treated with intravitreal anti-VEGF agents, while few studies reported worsening of non-perfusion with enlargement of foveal avascular zone (FAZ). Regarding peripheral ischemia, studies using wide-field-FFA demonstrated an improvement or stability in non-perfusion areas after anti-VEGF treatment. However, the use of wide-field-OCTA revealed no signs of re-perfusion of retinal vessels post anti-VEGF treatment. Further prospective studies with long follow-up and large sample size are still needed to draw solid conclusions.

Choroidal thickness and vessel pattern in myopic eyes with dome-shaped macula.

AIM: To analyse the choroidal thickness (CT) and vessel pattern of myopic patients with dome-shaped macula (DSM) and their association with the DSM axis and serous retinal detachment (SRD). METHODS: Retrospective study. The CT and vessel pattern were assessed on optical coherence tomography (OCT), OCT-angiography and ultra-wide-field photography. RESULTS: 27 eyes of 18 subjects (mean age: 65 years) were included. Compared with the 11 eyes (41%) with horizontal DSM, the 16 eyes (59%) with vertical DSM had a shorter axial length (25.8±2 mm vs 28.3±2.5 mm; p=0.01), a higher mean macular bulge height (624.4±207 µm vs 255.4±160.3 µm; p=0.0001) and a thicker CT (183.1±91.1 µm vs 72±38.3 µm; p<0.001). Large choroidal vessels crossed the macular area in 75% of eyes with vertical DSM vs 27% of eyes with horizontal DSM (p=0.02), whereas a watershed zone framing the macula was more often seen in horizontal DSM (72% vs 25%, p=0.02). Thirteen eyes (48%) had an SRD that was not associated with the DSM axis, the mean bulge height, the CT or the vessel pattern. CONCLUSION: The presence of an SRD did not correlate with the DSM axis, the CT or the vessel pattern. However, the rate of large choroidal vessels crossing the macula was higher in vertical DSM than in horizontal DSM.