Sight threatening diabetic retinopathy in patients with macular telangiectasia type 2.

PURPOSE: Although diabetes is highly prevalent in patients with MacTel, progression to severe non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR) is rarely reported. We report multimodal imaging features of sight-threatening diabetic retinopathy (STDR) in eyes with macular telangiectasia type 2 (MacTel). METHODS: Retrospective case series of seven participants of the MacTel Study at the Moorfields Eye Hospital NHS Foundation Trust study site and one patient from the Institute of Retina and Vitreous of Londrina, Brazil. Sight threatening diabetic retinopathy was defined as severe NPDR, PDR or diabetic macular edema. RESULTS: We report imaging features of 16 eyes of eight patients (7/8, 87.5% female) with diagnoses of MacTel and type 2 diabetes mellitus with STDR. Mean (SD) age was 56 (8.3) years. Patients were followed-up for a mean time of 9.1 (4.7) years. A total of 10/16 (62.5%) eyes showed PDR and 2/16 (12.5%) eyes presented a macular epiretinal neovascularization. CONCLUSIONS: People with diabetes mellitus and MacTel may not be protected from STDR as previously reported. Although the two diseases rarely co-exist, regular monitoring for diabetic retinopathy progression is recommended according to baseline retinopathy severity grades in line with established international guidelines. The presence of MacTel may not modify extended screening intervals, but there is no current evidence. The limited case series in the literature support treatment for complications and should follow the standard of care for either condition. Due to dual pathology, reactivation may be difficult to diagnose on standard imaging and multimodal imaging is recommended.

Choroidal ischemia as one cardinal sign in giant cell arteritis.

PURPOSE: To describe chorioretinal signs in a case series of Giant Cell Arteritis (GCA). METHODS: This is a multicenter retrospective observational case series with GCA that presented with a headache and an abrupt, unilateral loss in vision. Workup included temporal artery biopsies, intravenous fluorescein angiography, optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), blood levels of erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: There are a total of 8 GCA instances presented. Average age was 74.5. (Range 68-83 years). The patients reported that one eye's visual loss had suddenly started, along with a fresh headache and other systemic symptoms. Eight patients exhibited choroidal ischemia, five paracentral acute middle maculopathy (PAMM) lesions, five cotton wool spots, four anterior ischemic optic neuropathy, and one central retinal arterial occlusion at the time of presentation. The average ESR at presentation was 68 mm/hr (range 4-110), and 4/6 individuals had a significant increase. The mean CRP level was 6.2 mg/dL (range 2.0-15.4), and the level was always over the normal range. All patients' temporal artery biopsies were positive. CONCLUSION: Alongside PAMM lesions, cotton wool spots, anterior ischemic optic neuropathy, and central retinal artery occlusion, choroidal ischemia is a key angiographic indicator in the diagnosis of GCA. It may be crucial to recognize these typical ischemic chorioretinal signs while diagnosing GCA.

The Flavonoid Hesperidin Methyl Chalcone Targets Cytokines and Oxidative Stress to Reduce Diclofenac-Induced Acute Renal Injury: Contribution of the Nrf2 Redox-Sensitive Pathway.

Hesperidin is derived from citrus fruits among other plants. Hesperidin was methylated to increase its solubility, generating hesperidin methyl chalcone (HMC), an emerging flavonoid that possess anti-inflammatory and antioxidant properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a powerful regulator of cellular resistance to oxidant products. Previous data evidenced HMC can activate Nrf2 signaling, providing antioxidant protection against diverse pathological conditions. However, its effects on kidney damage caused by non-steroidal anti-inflammatory drugs (NSAIDs) have not been evaluated so far. Mice received a nephrotoxic dose of diclofenac (200 mg/kg) orally followed by intra-peritoneal (i.p.) administration of HMC (0.03-3 mg/kg) or vehicle. Plasmatic levels of urea, creatinine, oxidative stress, and cytokines were assessed. Regarding the kidneys, oxidative parameters, cytokine production, kidney swelling, urine NGAL, histopathology, and Nrf2 mRNA expression and downstream targets were evaluated. HMC dose-dependently targeted diclofenac systemic alterations by decreasing urea and creatinine levels, and lipid peroxidation, as well as IL-6, IFN-γ, and IL-33 production, and restored antioxidant properties in plasma samples. In kidney samples, HMC re-established antioxidant defenses, inhibited lipid peroxidation and pro-inflammatory cytokines and upregulated IL-10, reduced kidney swelling, urine NGAL, and histopathological alterations. Additionally, HMC induced mRNA expression of Nrf2 and its downstream effectors HO-1 and Nqo1, as well as reduced the levels of Keap1 protein detected in renal tissue. The present data demonstrate HMC is a potential compound for the treatment of acute renal damage caused by diclofenac, a routinely prescribed non-steroidal anti-inflammatory drug.

Birdshot retinochoroiditis in Brazil: a multicenter review of 40 patients.

BACKGROUND: Birdshot retinochoroiditis (BRC) is a rare and chronic bilateral uveitis mostly found in Caucasians. As few data are available about the clinical course of BRC in Hispanic patients, we aimed to report the clinical findings and the evolution of BRC in Brazilian patients. METHODS: This retrospective cohort multicenter nationwide study was performed by analyzing the records of patients with BRC diagnoses from Brazilian ophthalmological centers from April 1995 to May 2020. RESULTS: Forty patients (80 eyes) with a diagnosis of BRC were evaluated. The mean age was 53 years, and there was no sex predominance. All tested patients (34/40) were positive for HLA-A29. The diagnosis of BRC was made following the Levinson et al. criteria, and all ancillary tests were performed to exclude differential diagnoses. Clinical signs and symptoms, such as complications and treatment, were described. CONCLUSIONS: BRC evolution in Brazilian patients seems to have some peculiarities that diverge from the published literature available about Caucasians, as AS inflammation is higher in this population.

Intense Acute Swimming Induces Delayed-Onset Muscle Soreness Dependent on Spinal Cord Neuroinflammation.

Unaccustomed exercise involving eccentric contractions, high intensity, or long duration are recognized to induce delayed-onset muscle soreness (DOMS). Myocyte damage and inflammation in affected peripheral tissues contribute to sensitize muscle nociceptors leading to muscle pain. However, despite the essential role of the spinal cord in the regulation of pain, spinal cord neuroinflammatory mechanisms in intense swimming-induced DOMS remain to be investigated. We hypothesized that spinal cord neuroinflammation contributes to DOMS. C57BL/6 mice swam for 2 h to induce DOMS, and nociceptive spinal cord mechanisms were evaluated. DOMS triggered the activation of astrocytes and microglia in the spinal cord 24 h after exercise compared to the sham group. DOMS and DOMS-induced spinal cord nuclear factor κB (NFκB) activation were reduced by intrathecal treatments with glial inhibitors (fluorocitrate, α-aminoadipate, and minocycline) and NFκB inhibitor [pyrrolidine dithiocarbamate (PDTC)]. Moreover, DOMS was also reduced by intrathecal treatments targeting C-X3-C motif chemokine ligand 1 (CX3CL1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß or with recombinant IL-10. In agreement, DOMS induced the mRNA and protein expressions of CX3CR1, TNF-α, IL-1ß, IL-10, c-Fos, and oxidative stress in the spinal cord. All these immune and cellular alterations triggered by DOMS were amenable by intrathecal treatments with glial and NFκB inhibitors. These results support a role for spinal cord glial cells, via NFκB, cytokines/chemokines, and oxidative stress, in DOMS. Thus, unveiling neuroinflammatory mechanisms by which unaccustomed exercise induces central sensitization and consequently DOMS.

The citrus flavanone naringenin attenuates zymosan-induced mouse joint inflammation: induction of Nrf2 expression in recruited CD45+ hematopoietic cells.

BACKGROUND: Naringenin is a biologically active analgesic, anti-inflammatory, and antioxidant flavonoid. Naringenin targets in inflammation-induced articular pain remain poorly explored. METHODS: The present study investigated the cellular and molecular mechanisms involved in the analgesic/anti-inflammatory effects of naringenin in zymosan-induced arthritis. Mice were pre-treated orally with naringenin (16.7-150 mg/kg), followed by intra-articular injection of zymosan. Articular mechanical hyperalgesia and oedema, leucocyte recruitment to synovial cavity, histopathology, expression/production of pro- and anti-inflammatory mediators and NFκB activation, inflammasome component expression, and oxidative stress were evaluated. RESULTS: Naringenin inhibited articular pain and oedema in a dose-dependent manner. The dose of 50 mg/kg inhibited leucocyte recruitment, histopathological alterations, NFκB activation, and NFκB-dependent pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-33), and preproET-1 mRNA expression, but increased anti-inflammatory IL-10. Naringenin also inhibited inflammasome upregulation (reduced Nlrp3, ASC, caspase-1, and pro-IL-1ß mRNA expression) and oxidative stress (reduced gp91phox mRNA expression and superoxide anion production, increased GSH levels, induced Nrf2 protein in CD45+ hematopoietic recruited cells, and induced Nrf2 and HO-1 mRNA expression). CONCLUSIONS: Naringenin presents analgesic and anti-inflammatory effects in zymosan-induced arthritis by targeting its main physiopathological mechanisms. These data highlight this flavonoid as an interesting therapeutic compound to treat joint inflammation, deserving additional pre-clinical and clinical studies.

OUTCOMES OF ANTI-VEGF THERAPY IN CHOROIDAL NEOVASCULARIZATION AFTER MACULAR SURGERY.

PURPOSE: To report treatment outcomes of anti-vascular endothelial growth factor (VEGF) therapy in choroidal neovascularization (CNV) presenting after macular surgery. METHODS: Retrospective analysis of 7 eyes of 7 patients, who were diagnosed to have CNV after macular surgery and were treated with anti-vascular endothelial growth factor therapy. Collected data included demographic details; history of present illness; surgical procedure; and clinical examination including visual acuity at presentation and follow-up with imaging and management. Main outcome measures were resolution of CNV activity at the last follow-up. Secondary outcomes included change in visual acuity at final follow-up from baseline, number of injections, treatment free interval, and adverse events. RESULTS: Seven eyes of 7 patients (2 females and 5 males), which underwent macular surgery (4 macular hole repairs and 3 epiretinal membrane (ERM) removal), were included in this study. Two eyes had drusen at the time of surgery; however, five eyes had no preexisting conditions. Mean interval between surgery and CNV development was 21.07 ± 38.55 months (range, 2 months-9 years). All patients had undergone intravitreal anti-vascular endothelial growth factor injections (range, 2-15; mean number: 5.85) with one eye requiring additional photodynamic therapy (PDT) and focal laser. Visual acuity was unchanged with inactive CNV at the last visit in all eyes after anti-vascular endothelial growth factor therapy. The mean follow-up duration after the development of CNV was 35.5 months (range, 6.5 months-8 years). CONCLUSION: Choroidal neovascularization occurring after otherwise successful macular surgery is uncommon with unknown predisposing factors. This entity appears to have poor visual outcome with currently available anti-vascular endothelial growth factor therapy.

Naringenin Eye Drops Inhibit Corneal Neovascularization by Anti-Inflammatory and Antioxidant Mechanisms.

Purpose: To investigate the effect of naringenin eye drops in corneal neovascularization induced by alkali (1 N NaOH) burn in mice. Methods: Corneal neovascularization in the right eye of male Swiss mice was induced by alkali. Treatment with naringenin eye drops (0.08-80 µg; 8 µL of 0.01-10 g/L solution) or vehicle (saline) started 2 days before corneal neovascularization was induced and was performed twice a day. Mice were treated up until the time animals were euthanized and cornea tissue was collected for testing, which was 2, 4, and 6 hours after alkali stimulus for cytokine and antioxidant capacity measurements, and 3 and/or 7 days after alkali stimulus for the assessment of corneal epithelial thickness and neovascularization, neutrophil, and macrophage recruitment, and vascular endothelial growth factor (Vegf), platelet-derived growth factor (Pdgf), matrix metalloproteinase-14 (Mmp14), and pigment epithelium-derived factor (Pedf) mRNA expression. Results: Naringenin eye drops inhibited alkali burn-induced neutrophil (myeloperoxidase activity and recruitment of Lysm-GFP+ cells) and macrophage (N-acetyl-ß-D glucosaminidase activity) recruitment into the eye, decrease in epithelial thickness, and neovascularization in the cornea. Further, naringenin inhibited alkali-induced cytokine (IL-1ß and IL-6) production, Vegf, Pdgf, and Mmp14 mRNA expression, and the reduction of ferric reducing antioxidant power and Azinobis-(3-Ethylbenzothiazoline 6-Sulfonic acid) radical scavenging capacity as well as increased the reduced glutathione and protein-bound sulfhydryl groups levels. Conclusions: Collectively, these results indicate that naringenin eye drops are protective in alkali-induced corneal burn by inhibiting leukocyte recruitment, the proangiogenic factor expression, inflammatory cytokine production, and loss of antioxidant defenses.

Multicenter, Randomized Clinical Trial to Assess the Effectiveness of Intravitreal Injections of Bevacizumab, Triamcinolone, or Their Combination in the Treatment of Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of combined bevacizumab-triamcinolone intravitreal injection in the treatment of diabetic macular edema (DME) compared to monotherapy. PATIENTS AND METHODS: At eight clinical sites, 111 patients with DME were randomly assigned to receive an intravitreal injection of bevacizumab (Avastin; Genentech, South San Francisco, CA), triamcinolone (Ophthalmos Pharmaceutical Industry, São Paulo-SP, Brazil), or their combination. The primary outcome was visual acuity (VA) at 6 months' follow-up. RESULTS: The average number of injections was 3.2 in the bevacizumab group, 2.4 in the combined group, and 2.1 in the triamcinolone group. All groups presented with improvements in VA (P < .001); however, no differences between groups were observed (P = .436). Mean reduction in central retinal thickness was statistically different only between the triamcinolone and bevacizumab groups (P < .015). CONCLUSION: Mono- or combination therapy was effective for DME treatment. No synergistic effects were observed; however, triamcinolone alone or a drug combination may reduce the number of injections required when compared to bevacizumab alone. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:734-740.].

SURGICAL OUTCOMES AND COMPLICATIONS OF RHEGMATOGENOUS RETINAL DETACHMENT IN EYES WITH CHORIORETINAL COLOBOMA: The Results of the KKESH International Collaborative Retina Study Group.

PURPOSE: To study the outcomes of management of rhegmatogenous retinal detachment in eyes with chorioretinal colobomas. METHODS: A retrospective review of 119 patients (119 eyes) with chorioretinal colobomas who underwent surgical repair for rhegmatogenous retinal detachment was performed. Data were collected on the site of the retinal break, type of surgery, anatomical success, and complications. RESULTS: The most common location of the primary retinal break was the intercalary membrane in 58.8% of eyes. The most common surgical intervention was vitrectomy with endolaser and silicone oil tamponade (77.3% of eyes). Final anatomical success was achieved in 87.4% of eyes. Anatomical success was significantly higher in eyes that received long-acting tamponade (P = 0.006). Cryotherapy was significantly associated with failure of primary vitrectomy (P = 0.028). Placement of an encircling band did not affect anatomical outcomes (P = 0.75). Most of the eyes (60%) with recurrent retinal detachment after primary vitrectomy had a primary break within the normal retina. CONCLUSION: The optimal option for managing retinal detachment in eyes with chorioretinal colobomas is pars plana vitrectomy with long-acting tamponade (silicone oil or octafluoropropane) and retinopexy to the edge of the coloboma and the primary breaks. Cryotherapy is associated with poor anatomical outcomes. An encircling band does not seem to affect the final anatomical outcome.

Immediate retinal detachment after laser in situ keratomileusis.

PURPOSE: We report a case of rhegmatogenous retinal detachment immediately (first postoperative day) after the refractive surgery of laser in situ keratomileusis (LASIK). CASE REPORT: A 50-year-old man underwent bilateral LASIK; on the first postoperative day, he presented with decreased visual acuity due to retinal detachment with vitreous hemorrhage in the left eye. There were two horseshoe tears posterior to the equator and one peripheral operculated hole, all temporally located. Four months later, he presented with vitreous hemorrhage and a horseshoe tear temporal posterior to the equator in the right eye. RESULTS: Surgical treatment was done, and the retina reattached immediately after surgery and remained stable thereafter in both eyes. Six months after surgery, visual acuity was 20/30 in the left eye and 20/40 in the right eye. CONCLUSION: Although the cause/effect relationship between LASIK and retinal detachment has not yet been established, occurrence of immediate postoperative retinal detachment may represent a strong temporal suggestion of its association.

Será justificável a cirurgia para prolifraçäo vítreo-retiniana após trauma perfurante ocular? / Is surgery for proliferative vitreoretinopathy following perforating ocular injury justifiable?

Objetivo: Determinar o prognóstico e a satisfação dos pacientes com trauma ocular perfurante que foram submetidos à cirurgia para proliferação Vitreo-retiniana (PVR). Métodos: Prontuários sessenta pacientes foram reavaliados para caracterizar a taxa de sucesso cirúrgico anatômico e funcional. Trinta pacientes foram selecionados de modo aleatório e questionados por telefone. Resultados: Houve melhora visual para a maioria dos pacientes (58,3 por cento) apresentavam a retina colada no fianl do seguimento. Em média 2,89 cirurgias foram realizadas por olho. Dezenove (63,3 por cento) pacientes afirmaram que voltariam a operar novamente e 14 (46,6 por cento) que o ganho de campo periférico foi de benefício. Conclusão: Essa forma de tratamento deve ser oferecida e a decisão final deve ser tomada pelo paciente bem orientado e seu médico.