High glucose induces an early and transient cytoprotective autophagy in retinal Müller cells.

PURPOSE: We investigated the autophagic response of rat Müller rMC-1 cells during a short-term high glucose challenge. METHODS: rMC-1 cells were maintained in 5 mM glucose (LG) or exposed to 25 mM glucose (HG). Western blot analysis was used to evaluate the expression levels of markers of autophagy (LC3-II, p62) and glial activation (AQP4), as well as the activation of TRAF2/JNK, ERK and AKT pathways. Autophagic flux assessment was performed using the autophagy inhibitor chloroquine. ROS levels were measured by flow cytometry using dichlorofluorescein diacetate. ERK involvement in autophagy induction was addressed using the ERK inhibitor FR180204. The effect of autophagy inhibition on cell viability was evaluated by SRB assay. RESULTS: Activation of autophagy was observed in the first 2-6 h of HG exposure. This early autophagic response was transient, not accompanied by an increase in AQP4 or in the phospho-activation of JNK, a key mediator of cellular response to oxidative stress, and required ERK activity. Cells exposed to HG had a lower viability upon autophagy inhibition by chloroquine, as compared to those maintained in LG. CONCLUSION: A short-term HG challenge triggers in rMC-1 cells a process improving the ability to cope with stressful conditions, which involves ERK and an early and transient autophagy activation.

Outer retina dysfunction and choriocapillaris impairment in type 1 diabetes.

To study the outer retina morpho-functional characteristics and the choriocapillaris (CC) features in type 1 diabetic (T1D) patients, with and without signs of diabetic retinopathy (NPDR and NoDR). Twenty-five NPDR and 18 NoDR eyes were imaged by Optical Coherence Tomography Angiography. Ellipsoid zone (EZ) "normalized" reflectivity and CC perfusion density parameters, as flow deficits number (FDn), flow deficit average area (FDa) and flow deficit percentage (FD%), were analysed. Multifocal electroretinogram (mfERG) response amplitude densities (RADs) were measured. Mean EZ "normalized" reflectivity, CC FDn and FD% values, were similar (p > 0.05) in both groups, FDa was significant greater (p > 0.05) in NPDR compared with NoDR eyes. MfERG-RADs were similar in both groups. NPDR eyes showed a significant (p < 0.05) linear correlation between RADs and both, CC FDa and FD%. The EZ "normalized" reflectivity was negatively correlated with CC FD% in NoDR eyes. In NPDR T1D eyes a significant relationship between abnormal outer retina functional responses and CC impairment was observed, while in NoDR eyes the photoreceptor reflectivity was correlated to CC abnormalities. The outer retina dysfunction in NPDR correlated to CC drop-out let hypothesize that the outer retinal elements are functionally impaired in proportion to the CC vascular supply deficit.

Aflibercept in persistent neovascular AMD: comparison of different treatment strategies in switching therapy.

PurposeTo evaluate the effects of aflibercept administered according to a pro re nata (PRN) or Fixed Regimen to patients with neovascular AMD and persistent intraretinal/subretinal fluid (IRF/SRF) despite three consecutive ranibizumab injections.MethodsPatients were switched to aflibercept injection (IVA) administered according to a PRN or to a fixed regimen for 1 year in two different retina centers. At baseline each patient underwent a complete ophthalmologic evaluation, including best-corrected visual acuity assessment (BCVA ETDRS chart), fluorescein, and indocyanine green angiography and OCT.ResultsEach group included 36 eyes. After 1 year the PRN group showed BCVA stabilization (63 vs 60 letters, P=0.33), whereas fixed regimen group showed significant BCVA improvement (68 vs 71, P=0.008). The median central retinal thickness decreased by 94 µm in the PRN (P=0.002) and by 148 µm in the fixed regimen group (P≤0.001). Complete IRF/SRF reabsorption was found in 58% of eyes in the PRN and in 42% of eyes in the fixed regimen group. At 1-year visit, the percentage of eyes with pigment epithelium detachment did not significantly decrease, but a height reduction was recorded in both groups. The median number of IVA was 3.5 in the PRN and 7 in the fixed regimen group.ConclusionThe switch to aflibercept with both treatment strategies enabled improvement in morphological parameters and stabilization of visual acuity. BCVA improvement and reduction in vision loss with reduction in retinal thickness, fluid and PED height was achieved with the fixed regimen in previously treated nAMD after 1 year.

Choroidal neovascularization in angioid streaks and pseudoxanthoma elasticum: 1 year follow-up.

PURPOSE: To report the efficacy of intravitreal injection of bevacizumab 1.25 mg (IVB) in the treatment of choroidal neovascularization (CNV) secondary to angioid streaks (AS). METHODS: Case review of two patients with CNV secondary to AS treated with three IVB with a 1-year follow up. RESULTS: In both patients after 1 year fluorescein angiography and optical coherence tomography showed complete inactivity of the CNV and the ophthalmologic examination revealed stabilization of the visual acuity. CONCLUSIONS: The IBV appeared to be an effective and safe treatment for CNV secondary to AS resulting in a long-term CNV inactivation. Further long-term studies in this type of lesion are desirable.

Serotonin syndrome caused by olanzapine and clomipramine.

We describe a case of severe serotonin syndrome. The patient was simultaneously taking the atypical antidepressant olanzapine and a tricyclical antidepressant, clomipramine. Symptoms included altered mental state resulting in coma, myoclonus, hyperreflexia, diaphoresis, diarrhoea, disorientation and fever. After suspension of antidepressant drugs, intensive symptomatic treatment and administration of biperiden and cyproheptadine, the patient's condition improved.

Photodynamic therapy outcomes in a case of macular choroidal neovascularization secondary to Candida endophthalmitis.

PURPOSE: To evaluate the effects on visual function and choroidal neovascularization (CNV) progression in a case of subretinal CNV due to Candida endophthalmitis treated with a combination of photodynamic therapy (PDT) and drugs. METHODS: A 28-year-old one-eyed woman with CNV in the right eye came to our observation. The CNV developed as a consequence of Candida endophthalmitis. The CNV was treated with six PDT treatments with verteporfin in association with systemic steroid therapy with prednisone (100 mg/day to reduce) and fluconazole (800 mg/day to reduce). Visual acuity (VA) was assessed in pre-PDT conditions and after six PDT treatments (24 months of follow-up). RESULTS: Pre-PDT VA was 20/125; after 24 months of follow-up, six PDT re-treatments, and pharmacologic therapy, VA was stabilized at 20/100. CONCLUSIONS: In our case, associated PDT and drug therapies were safe and useful to maintain VA and to arrest CNV progression in the foveal region after 2 years of follow-up.

Quality of vision: A consensus building initiative for a new ophthalmologic concept.

PURPOSE: Many studies have addressed the quantification of visual acuity, and the conventional method of measuring it has so far demonstrated serious limitations. Vision testing requires new methods that can more precisely express the quality of vision as perceived by the patient. METHODS: This study employed the Delphi method of consensus building. Concepts associated with quality of vision (QoV) were identified by a board of experts and proposed to participating specialists in two subsequent questionnaires. Upon receipt of the completed questionnaires, the replies were classified to determine the building blocks of a consensus. RESULTS: By analyzing the replies to the two questionnaires, the authors determined the key elements of QoV on which a consensus was found among the respondents. CONCLUSIONS: A consensus was reached on the opinion that the quantification of visual acuity by traditional means is inadequate for investigating QoV. Although visual acuity is still a basic element for testing, the experts believe that contrast sensitivity, reading speed, and microperimetry are additional parameters necessary for quantifying QoV. The use of a psychometric questionnaire on visual function could allow a better interpretation of visual impairment.

Use of recombinant activated factor VII in a case of severe postpartum haemorrhage.

We describe the case of a 24 year old woman, affected by haemorrhagic shock due to post-partum uterine atony, who underwent an emergency hysterectomy with persistent postoperative bleeding, successfully treated with recombinant activated factor VII (Novoseven).

Visual acuity and macular sensitivity in myopic eyes before and after laser in situ keratomileusis.

PURPOSE: To evaluate the changes in visual acuity (VA) and in macular sensitivity in myopic eyes subjected to laser in situ keratomileusis (LASIK) refractive surgery. METHODS: In 38 myopic eyes, VA by Snellen's table and macular sensitivity by scanning laser ophthalmoscope (SLO) microperimetry were assessed before and after 24 weeks after LASIK surgery. The myopic eyes were divided into three age-matched groups: Group A = from -5 diopters (D) to -7 D and normal SLO-macular sensitivity (15 eyes); Group B = from -8 D to -16 D and normal SLO-macular sensitivity (9 eyes); and Group C = from -8 D to -16 D and abnormal SLO-macular sensitivity. RESULTS: Group A and B eyes, at the first week after LASIK surgery, we observed a significant analysis of variance, p<0.01) reduction in VA and SLO-macular sensitivity with respect to baseline values, while after 12 and 24 weeks no differences (p>0.01) were found when compared to baseline. In Group C patients, at 1 and 4 weeks after surgical treatment, we observed a significant (p<0.01) reduction in VA and SLO-macular sensitivity with respect to baseline values. At 12 and 24 weeks the values of VA were reduced, but not significantly (p>0.01), while values of SLO-macular sensitivity were still significantly (p<0.01) reduced. CONCLUSIONS: LASIK could induce a reduction in VA and SLO-macular sensitivity in all myopic eyes during the 4 weeks following the surgery. This reduction is still present after 24 weeks only in eyes with the highest preoperative degree of myopia combined with the greatest reduction in macular sensitivity.

Use of activated protein C in a case of paediatric septic shock.

We describe a clinical case of a 7 year old girl, affected by peritonitis, septic shock and multiorgan failure, treated successfully with drotrecogin alpha associated with conventional therapy.

Visual acuity and macular sensitivity in myopic eyes before and after laser in situ keratomileusis.

PURPOSE: To evaluate the changes in visual acuity (VA) and in macular sensitivity in myopic eyes subjected to laser in situ keratomileusis (LASIK) refractive surgery. METHODS: In 38 myopic eyes, VA by Snellen's table and macular sensitivity by scanning laser ophthalmoscope (SLO) microperimetry were assessed before and after 24 weeks after LASIK surgery. The myopic eyes were divided into three age-matched groups: Group A = from -5 diopters (D) to -7 D and normal SLO-macular sensitivity (15 eyes); Group B = from -8 D to -16 D and normal SLO-macular sensitivity (9 eyes); and Group C = from -8 D to -16 D and abnormal SLO-macular sensitivity. RESULTSGroup A and B eyes, at the first week after LASIK surgery, we observed a significant analysis of variance, p<0.01) reduction in VA and SLO-macular sensitivity with respect to baseline values, while after 12 and 24 weeks no differences (p>0.01) were found when compared to baseline. In Group C patients, at 1 and 4 weeks after surgical treatment, we observed a significant (p<0.01) reduction in VA and SLO-macular sensitivity with respect to baseline values. At 12 and 24 weeks the values of VA were reduced, but not significantly (p>0.01), while values of SLO-macular sensitivity were still significantly (p<0.01) reduced. CONCLUSIONS: LASIK could induce a reduction in VA and SLO-macular sensitivity in all myopic eyes during the 4 weeks following the surgery. This reduction is still present after 24 weeks only in eyes with the highest preoperative degree of myopia combined with the gre a test reduction in macular sensitivity.

[Pharmacological sympathetic block in complex regional pain syndrome]. / Blocco farmacologico del simpatico nella Complex Regional Pain Syndrome.

PURPOSE: The Complex Regional Pain Syndrome (CRPS) is a chronic pain state provoked by lesions of the soft tissues or of the bony tissues (type CRPS-I or reflex sympathetic dystrophy-RSD) or by lesions of the nerves (type CRPS-II or causalgia) with vegetative alterations (perspiration, vasomotory alterations) and trophic alterations (bony cutaneous atrophy, alopecia, articular contractures). The pharmacological block of the sympathetic nerves through a peripheral vein is inserted in the multidisciplinary approach that characterizes the therapy of this syndrome. MATERIALS AND METHODS: A retrospective survey was carried out on a group of 185 patients affected by RDS/CRPS with block of the sympathetic nerves through a peripheral vein with guanethidine. Superior limb: Inflation of the tourniquet till disappearance of the radial wrist. Cannulation of a peripheral vein with Butterfly needle n. 23. Guanethidine 10 mg, lidocaine 20 mg, sodic heparin 500 u.i, NaCl 0.9% 20 ml. Injection in 5 minutes. Permanence of the pneumatic tourniquet inflated above systolic blood pressure for 15 minutes. Deflation slowly. Inferior limb: Inflation of the tourniquet till disappearance of the pedidium wrist. Cannulation of a peripheral vein with Butterfly needle n. 23. Guanethidine 20 mg, lidocaine 40 mg, sodic heparin 1000 u.i, NaCl 0.9% 40 ml. Injection in 5 minutes. Permanence of the pneumatic tourniquet inflated above systolic blood pressure for 15 minutes. Deflation slowly. RESULTS: The first stage (hyperemic) showed the highest incidence of remissions: (83, 33%). Even in the second stage (dystrophic) the answer to the therapy has been fundamentally positive: (53, 68%). In the third stage (atrophic) the results have been more modest: (8, 33%). CONCLUSIONS: The block of sympathetic system with guanethidine is still an important method in the therapy of the CRPS; in fact it is surely less invading than the blocks of the stellate ganglion or of the lumbar sympathetic.

Scanning laser ophthalmoscope microperimetry.

In this article, the methodologies and clinical applications of microperimetry performed by scanning laser ophthalmoscope (SLO) are described. This technique provides functional results by direct visualization of the macular area. We present the most interesting data about clinical applications in ocular pathology. SLO microperimetry is a new diagnostic tool in ophthalmic practice. It permits an exact, point-to-point correspondence between fundus image and perimetric results, impossible to achieve by projection perimetry, so representing the most suitable device for simultaneous fundus imaging and psychophysical testing. Microperimetry is performed by SLO (Rodenstock),1 which permits other applications. SLO microperimetry allows the real-time functional study of retinal sensitivity by direct ophthalmoscopic control of the retinal surface. Foveal or excentric fixation can be assessed as well. Instability of fixation during computerized perimetry is a possible misleading factor resulting in unexplainable findings, especially in eyes with decreased visual acuity. The main characteristic of microperimetry is the ability to see the stimuli presented on the retina in real time: this permits an accurate monitoring of fixation and correlation of anatomical or pathological features directly with retinal function.

Scanning laser ophthalmoscopy in the early diagnosis of vitreoretinal interface syndrome.

BACKGROUND: The purpose of this study was to estimate if and to what extent scanning laser ophthalmoscopy can help in the early diagnosis and follow-up management of the vitreoretinal interface syndrome, which includes disorders such as cellophane maculopathy, pseudomacular hole, macular pucker, and macular hole. METHODS: The 35 fellow eyes of 35 patients with vitreoretinal interface syndromes in the first eye underwent scanning laser ophthalmoscopy microperimetry and argon, helium-neon, and infrared scanning laser ophthalmoscopy. Fellow eyes were defined as clinically positive or negative for vitreoretinal interface syndrome. Fellow eyes then were classified based on scanning laser ophthalmoscopy techniques. Patients were observed for an average of 18 months (range, 10-26 months). RESULTS: Thirty-two of the 35 fellow eyes were classified as clinically negative, and three of the 35 were classified as clinically positive. Fifteen of the 32 clinically negative fellow eyes were redefined as positive on scanning laser ophthalmoscopy. None of the clinically positive eyes proved to be negative on scanning laser ophthalmoscopy. During the average follow-up period (18 months), the condition of five of 18 fellow eyes that were positive on scanning laser ophthalmoscopy worsened. None of the 17 eyes that were negative on scanning laser ophthalmoscopy worsened. CONCLUSION: Scanning laser ophthalmoscopy can produce beautifully clear images of structures that are otherwise difficult to see and document, such as posterior hyaloid and the inner retinal layers. Despite a relatively limited number of cases and the short duration of the follow-up period, the present study suggests that scanning laser ophthalmoscopy has good sensitivity and specificity for the early diagnosis of vitreoretinal interface syndromes.

Randomized clinical trial of tamoxifen plus sequential CMF chemotherapy versus tamoxifen alone in postmenopausal women with advanced breast cancer.

Eighty-eight postmenopausal women with metastatic breast cancer, in whom estrogen receptors (ER) were positive or unknown, were treated on a controlled trial to determine the effectiveness of tamoxifen and to assess the therapeutic advantage of sequentially adding low-dose cyclophosphamide-methotrexate-5-fluorouracil (CMF) chemotherapy in tamoxifen responders. Patients with known ER negative status were not studied. After the initial 12-week treatment with tamoxifen alone, 60% of ER positive patients achieved complete or partial response as did 35% in whom ER were unknown. Response status further improved in 18% randomized to continue tamoxifen alone vs 31% in whom CMF was added to tamoxifen. There were no statistically significant differences in time to the development of progressive disease or survival between the ER positive and ER unknown patients or between the tamoxifen and tamoxifen plus CMF groups. We conclude that inability to determine ER status should not prejudice against the use of tamoxifen in postmenopausal patients with advanced breast cancer. No benefit has been demonstrated from the addition of CMF chemotherapy in tamoxifen responders.