Evaluation of Macular Thickness Changes after Uncomplicated Phacoemulsification Surgery in Healthy Subjects and Diabetic Patients without Retinopathy by Spectral Domain OCT.

PURPOSE: To assess differences in the evolution of macular thickness after uncomplicated phacoemulsification surgery between non-diabetic subjects and patients with diabetes mellitus (DM) without diabetic retinopathy (DR), using Spectral Domain OCT (SD-OCT). METHODS: We performed a unicentric prospective study including one hundred and thirty-one eyes of 70 patients divided into two groups-34 well-controlled DM patients without DR and 36 non-diabetic subjects-who underwent phacoemulsification for cataract surgery. Eyes that developed pseudophakic cystoid macular edema (PCME) were excluded from the study, leaving us with 64 patients. Macular thickness was analyzed using Cirrus HD-OCT (Macular Cube 512 × 128 protocol) preoperatively and on postoperative days 7, 30, 90, and 180. For cases with information available for both eyes, one eye was randomly selected for analysis. RESULTS: A total of 64 eyes from 64 patients were analyzed in this study. The mean value of HbA1c in the diabetic group was 7%. After uncomplicated cataract surgery, patients showed no increase of the foveal, parafoveal, and perifoveal retinal thickness on postoperative day 7. However, thickness values increased on days 30, 90, and 180 after surgery in both groups, and peak at 90 days. There was no difference in macular thickness before or after surgery between DM and non-diabetic patients (p = 0.540). CONCLUSION: Macular thickness increases up to 6 months after uncomplicated cataract surgery in both DM patients without DR and non-diabetic subjects, with no differences between increases in both groups.

The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world.

PURPOSE: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. METHODS: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. RESULTS: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). CONCLUSION: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.

Plasma Rich in Growth Factors (PRGF) Increases the Number of Retinal Müller Glia in Culture but Not the Survival of Retinal Neurons.

Plasma rich in growth factors (PRGF) is a subtype of platelet-rich plasma (PRP) that stimulates tissue regeneration and may promote neuronal survival. It has been employed in ophthalmology to achieve tissue repair in some retinal pathologies, although how PRGF acts in the retina is still poorly understood. As a part of the central nervous system, the retina has limited capacity for repair capacity following damage, and retinal insult can provoke the death of retinal ganglion cells (RGCs), potentially producing irreversible blindness. RGCs are in close contact with glial cells, such as Müller cells, that help maintain homeostasis in the retina. In this study, the aim was to determine whether PRGF can protect RGCs and whether it increases the number of Müller cells. Therefore, PRGF were tested on primary cell cultures of porcine RGCs and Müller cells, as well as on co-cultures of these two cell types. Moreover, the inflammatory component of PRGF was analyzed and the cytokines in the different PRGFs were quantified. In addition, we set out to determine if blocking the inflammatory components of PRGF alters its effect on the cells in culture. The presence of PRGF compromises RGC survival in pure cultures and in co-culture with Müller cells, but this effect was reversed by heat-inactivation of the PRGF. The detrimental effect of PRGF on RGCs could be in part due to the presence of cytokines and specifically, to the presence of pro-inflammatory cytokines that compromise their survival. However, other factors are likely to be present in the PRGF that have a deleterious effect on the RGCs since the exposure to antibodies against these cytokines were insufficient to protect RGCs. Moreover, PRGF promotes Müller cell survival. In conclusion, PRGF hinders the survival of RGCs in the presence or absence of Müller cells, yet it promotes Müller cell survival that could be the reason of retina healing observed in the in vivo treatments, with some cytokines possibly implicated. Although PRGF could stimulate tissue regeneration, further studies should be performed to evaluate the effect of PRGF on neurons and the implication of its potential inflammatory role in such processes.

The Effect of Plasma Rich in Growth Factors on Microglial Migration, Macroglial Gliosis and Proliferation, and Neuronal Survival.

Plasma rich in growth factors (PRGF) is a subtype of platelet-rich plasma that has being employed in the clinic due to its capacity to accelerate tissue regeneration. Autologous PRGF has been used in ophthalmology to repair a range of retinal pathologies with some efficiency. In the present study, we have explored the role of PRGF and its effect on microglial motility, as well as its possible pro-inflammatory effects. Organotypic cultures from adult pig retinas were used to test the effect of the PRGF obtained from human as well as pig blood. Microglial migration, as well as gliosis, proliferation and the survival of retinal ganglion cells (RGCs) were analyzed by immunohistochemistry. The cytokines present in these PRGFs were analyzed by multiplex ELISA. In addition, we set out to determine if blocking some of the inflammatory components of PRGF alter its effect on microglial migration. In organotypic cultures, PRGF induces microglial migration to the outer nuclear layers as a sign of inflammation. This phenomenon could be due to the presence of several cytokines in PRGF that were quantified here, such as the major pro-inflammatory cytokines IL-1ß, IL-6 and TNFα. Heterologous PRGF (human) and longer periods of cultured (3 days) induced more microglia migration than autologous porcine PRGF. Moreover, the migratory effect of microglia was partially mitigated by: 1) heat inactivation of the PRGF; 2) the presence of dexamethasone; or 3) anti-cytokine factors. Furthermore, PRGF seems not to affect gliosis, proliferation or RGC survival in organotypic cultures of adult porcine retinas. PRGF can trigger an inflammatory response as witnessed by the activation of microglial migration in the retina. This can be prevented by using autologous PRGF or if this is not possible due to autoimmune diseases, by mitigating its inflammatory effect. In addition, PRGF does not increase either the proliferation rate of microglial cells or the survival of neurons. We cannot discard the possible positive effect of microglial cells on retinal function. Further studies should be performed to warrant the use of PRGF on the nervous system.

Comparative lipidomic analysis of mammalian retinal ganglion cells and Müller glia in situ and in vitro using High-Resolution Imaging Mass Spectrometry.

In order to better understand retinal physiology, alterations to which underlie some ocular diseases, we set out to establish the lipid signature of two fundamental cell types in the retina, Müller Glia and Retinal Ganglion Cells (RGCs). Moreover, we compared the lipid signature of these cells in sections (in situ), as well as after culturing the cells and isolating their cell membranes (in vitro). The lipidome of Müller glia and RGCs was analyzed in porcine retinal sections using Matrix Assisted Laser Desorption Ionization Imaging Mass Spectrometry (MALDI-IMS). Isolated membranes, as well as whole cells from primary cell cultures of RGCs and Müller glia, were printed onto glass slides using a non-contact microarrayer (Nano Plotter), and a LTQ-Orbitrap XL analyzer was used to scan the samples in negative ion mode, thereafter identifying the RGCs and Müller cells immunohistochemically. The spectra acquired were aligned and normalized against the total ion current, and a statistical analysis was carried out to select the lipids specific to each cell type in the retinal sections and microarrays. The peaks of interest were identified by MS/MS analysis. A cluster analysis of the MS spectra obtained from the retinal sections identified regions containing RGCs and Müller glia, as confirmed by immunohistochemistry in the same sections. The relative density of certain lipids differed significantly (p-value ≤ 0.05) between the areas containing Müller glia and RGCs. Likewise, different densities of lipids were evident between the RGC and Müller glia cultures in vitro. Finally, a comparative analysis of the lipid profiles in the retinal sections and microarrays identified six peaks that corresponded to a collection of 10 lipids characteristic of retinal cells. These lipids were identified by MS/MS. The analyses performed on the RGC layer of the retina, on RGCs in culture and using cell membrane microarrays of RGCs indicate that the lipid composition of the retina detected in sections is preserved in primary cell cultures. Specific lipid species were found in RGCs and Müller glia, allowing both cell types to be identified by a lipid fingerprint. Further studies into these specific lipids and of their behavior in pathological conditions may well help identify novel therapeutic targets for ocular diseases.

Efficacy and Safety of an Aflibercept Treat-and-Extend Regimen in Treatment-Naïve Patients with Macular Oedema Secondary to Central Retinal Vein Occlusion (CRVO): A Prospective 12-Month, Single-Arm, Multicentre Trial.

OBJECTIVES: To evaluate efficacy and safety of an aflibercept treat-and-extend (TAE) regimen in patients with macular oedema (MO) secondary to central retinal vein occlusion (CRVO). DESIGN SETTING AND PATIENTS: Phase IV, prospective, open-label, single-arm trial in 11 Spanish hospitals. Treatment-naïve patients with <6 month diagnosis of MO secondary to CRVO and best-corrected visual acuity (BCVA) of 73-24 ETDRS letters were included between 23 January 2015 and 17 March 2016. INTERVENTION: Intravitreal aflibercept 2 mg monthly (3 months) followed by proactive individualized dosing. MAIN OUTCOMES: Mean change in BCVA after 12 months. RESULTS: 24 eyes (24 patients) were included; mean (SD) age: 62.8 (15.0) years; 54.2% male; median (IQR) time since diagnosis: 7.6 (3.0, 15.2) days. Mean BCVA scores significantly improved between baseline (56.0 (16.5)) and Month 12 (74.1 (17.6)); mean (95% CI) change: 14.8 (8.2, 21.4); P=0.0001. Twelve (50.0%) patients gained ≥15 ETDRS letters. Foveal thickness improved between baseline (mean: 569.4 (216.8) µm) and Month 12 (mean 257.4 (48.4) µm); P < 0.0001. At Month 12, 8.3% patients had MO. The mean (SD) number of injections: 8.3 (3.0). No treatment-related AEs were reported. Five (20.8%) patients experienced ocular AEs. Two nonocular serious AEs were reported. CONCLUSIONS: An aflibercept TAE regimen improves visual acuity in patients with MO secondary to CRVO over 12 months with good tolerability.

The Retina of Osteopontin deficient Mice in Aging.

Osteopontin (OPN) is a secreted glycosylated phosphoprotein that influences cell survival, inflammation, migration, and homeostasis after injury. As the role of OPN in the retina remains unclear, this study issue was addressed by aiming to study how the absence of OPN in knock-out mice affects the retina and the influence of age on these effects. The study focused on retinal ganglion cells (RGCs) and glial cells (astrocytes, Müller cells, and resident microglia) in 3- and 20-month-old mice. The number of RGCs in the retina was quantified and the area occupied by astrocytes was measured. In addition, the morphology of Müller cells and microglia was examined in retinal sections. The deficiency in OPN reduces RGC density by 25.09% at 3 months of age and by 60.37% at 20 months of age. The astrocyte area was also reduced by 51.01% in 3-month-old mice and by 57.84% at 20 months of age, although Müller glia and microglia did not seem to be affected by the lack of OPN. This study demonstrates the influence of OPN on astrocytes and RGCs, whereby the absence of OPN in the retina diminishes the area occupied by astrocytes and produces a secondary reduction in the number of RGCs. Accordingly, OPN could be a target to develop therapies to combat neurodegenerative diseases and astrocytes may represent a key mediator of such effects.

Treatment of Exudative Age-related Macular Degeneration: Focus on Aflibercept.

A formulation of aflibercept for intravitreal injection (Eylea) is approved for the treatment of patients with exudative age-related macular degeneration (AMD). Aflibercept has a significantly higher affinity for Vascular endothelial growth factor (VEGF)-A compared with other monoclonal anti-VEGF antibodies. In addition to binding all VEGF-A isoforms, aflibercept also blocks other proangiogenic factors such as VEGF-B and placental growth factor. The VIEW 1 and 2 trials showed this drug achieves improved results in patients with exudative AMD similar to those obtained with monthly ranibizumab, using a bimonthly treatment regimen after a loading dose of three intravitreal injections, which translates to less use of healthcare resources. There is a subgroup of patients that present with persistent fluid after the loading dose that could benefit from monthly injections or personalized proactive treatment after the first year. In the second year of treatment, the Treat and Extend patterns can permit even more lengthening of the time between injections. More data are needed to confirm the optimal monitoring and retreatment dosing, to maintain long-term efficacy. Other preliminary data suggest that patients that do not respond to other anti-angiogenics and patients with special pathologies such as polypoidal choroidopathy or retinal angiomatous proliferation can improve upon switching to aflibercept. To date, the safety profile of aflibercept is excellent and is comparable to other anti-angiogenic treatments.

Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration.

Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that "treat and extend" and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR CHOROIDAL NEOVASCULARIZATION SECONDARY TO PATHOLOGIC MYOPIA: SIX YEARS OUTCOME.

PURPOSE: To report the visual outcome after 6-year follow-up in highly myopic eyes with choroidal neovascularization treated with anti-vascular endothelial growth factor drugs. METHODS: Retrospective, nonrandomized, multicenter, consecutive, and interventional case series. RESULTS: Seventy-eight patients were treated with intravitreal bevacizumab and 19 with ranibizumab. Mean age of the patients was 56.5 years (SD, 13.3). The average number of letters read was 56.7 (SD, 19.0) at baseline; 65.7 (SD, 18.4) at 12 months; 63.6 (SD, 20.6) at 24 months; 62.4 (SD, 21.4) at 36 months; 60.6 (SD, 22.0) at 48 months; 58.9 (SD, 22.9) at 60 months, and 58.4 (SD, 22.7) at 72 months (P < 0.01, between initial vs. 12, 24, and 36 months; P = 0.07, 0.3, and 0.5 between initial vs. 48, 60, and 72 months, respectively; Student's t-test paired data). The mean total number of intravitreal injections was 3.3 (SD, 2.3; range, 1-9). CONCLUSION: Bevacizumab and ranibizumab are effective therapies and show similar clinical effects in myopic eyes with choroidal neovascularization. Visual acuity gain is maintained at a 3-year follow-up. The improvement is no longer statistically significant at Years 4, 5, and 6.

Do nutritional supplements have a role in age macular degeneration prevention?

Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids ( ω -3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω -3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of ω -3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω -3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

A delphi study to detect deficiencies and propose actions in real life treatment of neovascular age-related macular degeneration.

Purpose. Spanish retina specialists were surveyed in order to propose actions to decrease deficiencies in real-life neovascular age macular degeneration treatment (nv-AMD). Methods. One hundred experts, members of the Spanish Vitreoretinal Society (SERV), were invited to complete an online survey of 52 statements about nv-AMD management with a modified Delphi methodology. Four rounds were performed using a 5-point Linkert scale. Recommendations were developed after analyzing the differences between the results and the SERV guidelines recommendations. Results. Eighty-seven specialists completed all the Delphi rounds. Once major potential deficiencies in real-life nv-AMD treatment were identified, 15 recommendations were developed with a high level of agreement. Consensus statements to reduce the burden of the disease included the use of treat and extend regimen and to reduce the amount of diagnostic tests during the loading phase and training technical staff to perform these tests and reduce the time between relapse detection and reinjection, as well as establishing patient referral protocols to outside general ophthalmology clinics. Conclusion. The level of agreement with the final recommendations for nv-AMD treatment among Spanish retinal specialist was high indicating that some actions could be applied in order to reduce the deficiencies in real-life nv-AMD treatment.

Spectral-domain optical coherence tomography study of macular structure as prognostic and determining factor for macular hole surgery outcome.

PURPOSE: To evaluate postoperative spectral-domain optical coherence tomography findings after macular hole surgery. METHODS: Retrospective, interventional, nonrandomized study. Overall, 164 eyes of 157 patients diagnosed with macular hole were operated on by vitrectomy and internal limiting membrane peeling. Preoperative and postoperative best-corrected visual acuity and spectral-domain optical coherence tomography images were obtained. Two groups were considered on the basis of the postoperative integrity of the back reflection line from the ellipsoid portion of the photoreceptor inner segment: group A (disruption of ellipsoid portion of the inner segment line, 60 eyes) and group B (restoration of ellipsoid portion of the inner segment line, 104 eyes). RESULTS: Logarithm of the minimum angle of resolution best-corrected visual acuity improved significantly after the surgery of macular hole from a mean preoperative value of 0.79 ± 0.37 (range, 0.15-2.00) to a mean postoperative value of 0.35 ± 0.31 (range, 0.00-1.30) at the last follow-up visit (P < 0.01). Best-corrected visual acuity improved significantly in the 2 groups analyzed (all P < 0.01). A larger improvement was found in group B than in group A (P < 0.01). CONCLUSION: Ellipsoid portion of the inner segment line reconstruction seems to be a good prognostic factor for visual rehabilitation after macular hole surgery.

Twelve-month outcome after one intravitreal injection of bevacizumab to treat myopic choroidal neovascularization.

PURPOSE: To report the changes during a 1-year follow-up in visual acuity and macular thickness in a series of highly myopic eyes with choroidal neovascularization treated with bevacizumab. METHODS: Retrospective and multicenter study including 107 highly myopic eyes from 107 patients (mean age, 55 years) with subfoveal or juxtafoveal choroidal neovascularization. All cases were treated by one intravitreous injection of 1.25 mg bevacizumab. Best-corrected visual acuity and macular thickness with the optical coherence tomography were evaluated at baseline and then monthly during 1 year. RESULTS: Logarithm of the minimum angle of resolution best-corrected visual acuity at baseline averaged 0.72 (standard deviation [SD], 0.43) versus 0.53 (SD, 0.41) at 1 year after treatment (P < 0.001). Logarithm of the minimum angle of resolution best-corrected visual acuity was 0.30 or better in 49 of 107 eyes (45%) at 1 year. Thirty-three eyes (30%) gained at least 3 Early Treatment Diabetic Retinopathy Study lines (15 letters) during the follow-up. In 43 eyes (40%), reinjections were necessary because signs of choroidal neovascularization activity were still evident. The mean number of reinjections was 0.8 (SD, 1.3). Best-corrected visual acuity improvement was better in the younger group (younger than 50 years). No adverse reactions were reported. CONCLUSION: One intravitreal bevacizumab injection seems to be an effective therapeutic approach to treat choroidal neovascularization in highly myopic eyes. Careful monitoring is necessary to assess the need for reinjections.

Comparative effects of six intraocular vital dyes on retinal pigment epithelial cells.

PURPOSE: To evaluate and compare the effects of the following dyes on human pigmented epithelial cells: indocyanine green (ICG), infracyanine green (IfCG), trypan blue (TB), bromophenol blue (BrB), patent blue (PB), and Brilliant Blue G (BBG). METHODS: ARPE-19 cells cultured in vitro were exposed to these dyes, and acute and chronic toxicity were evaluated. Cell viability was measured by colorimetry (MTT assay), morphology was observed by phase-contrast microscopy, membrane permeability (CMP) was evaluated by flow cytometry with propidium iodide (PI), and mitochondrial membrane potential (ΔΨm) was measured with 3,3'-dihexyloxacarbocyanine (DiOC(6)(3)). RESULTS: Each of the studied dyes exhibited toxicity after acute exposure at surgical doses. The presence of light often reduced cell viability, especially when measured 3 hours after incubation in the case of ICG, TB, BrB, and BBG. Morphologic changes were induced by ICG, IfCG, and BBG. Both CMP and ΔΨm were altered after exposure to surgical doses of ICG, TB, PB, and a fourfold surgical dose of BrB. Chronic exposure to residual amounts of some dyes was associated with reduced proliferation and even cell death. CONCLUSIONS: It appears to be prudent to use the lowest possible dose of each dye, to minimize the risk of toxic effects. This precaution may be particularly important in the case of BrB, which should not be used in excess of 0.5%. In addition, abundant irrigation of the vitreous cavity after surgery to completely remove traces of dye may be of crucial importance, particularly in the case of ICG, in minimizing chronic toxicity.

Beneficial effect of docosahexanoic acid and lutein on retinal structural, metabolic, and functional abnormalities in diabetic rats.

PURPOSE: To assess the effect of docosahexanoic acid (DHA) and lutein (both compounds with anti-inflammatory and antioxidant properties) on experimental diabetic retinopathy. METHODS: Male Wistar rats were studied: non-diabetic controls, untreated diabetic controls, and diabetic rats were treated with DHA and lutein or the combination of DHA + insulin and lutein + insulin for 12 weeks. Oxidative stress and inflammatory markers, apoptosis, and functional tests were studied to confirm biochemical and functional changes in the retina of diabetic rats. Malondialdehyde (MDA), glutathione concentrations (GSH), and glutathione peroxidase activity (GPx) were measured as oxidative stress markers. TUNEL assay and caspase-3 immunohistochemistry and electroretinogram were performed. RESULTS: Diabetes increases oxidative stress, nitrotyrosine concentrations, and apoptosis in the retina. At 12 weeks after onset of diabetes, total thickness of retinas of diabetic rats was significantly less than that in control rats. Specifically, the thickness of the outer and inner nuclear layers was reduced significantly in diabetic rats and demonstrated a loss of cells in the GCL. These retinal changes were avoided by the administration of insulin and DHA and lutein alone or in combination with insulin. Impairment of the electroretinogram (b-wave amplitude and latency time) was observed in diabetic rats. DHA and lutein prevented all these changes even under hyperglycemic conditions. CONCLUSIONS: Lutein and DHA are capable of normalizing all the diabetes-induced biochemical, histological, and functional modifications. Specifically, the cell death mechanisms involved deserve further studies to allow the proposal as potential adjuvant therapies to help prevent vision loss in diabetic patients.

Oxidative stress in rat retina and hippocampus after chronic MDMA ('ecstasy') administration.

The effects of MDMA administration on oxidative stress markers in rat eye and hippocampus, and the neuroprotective effects of the antioxidant 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6) have been studied. MDMA effects on liver were used for comparison with those in eye and hippocampus and to test CR-6 protective effects. Another goal was to test for apoptosis in retinal cells, as it is known that happens in liver and brain. After 1 week of ecstasy administration, malondialdehyde (MDA) concentration increased, glutathione peroxidase (GPx) activity and glutathione (GSH) content decreased in liver, as previously described. MDA concentration increased and GPx activity decreased in hippocampus; whereas no change was observed in GSH concentration. MDMA decreased ocular GSH concentration and GPx activity; no change was observed in MDA concentration. The number of TUNEL-positive nuclei increased significantly in rat retinas after 1 week of MDMA administration. CR-6 normalized the modifications in liver, hippocampus and retina mentioned above.

Photodynamic therapy in subfoveal and juxtafoveal idiopathic and postinflammatory choroidal neovascularization.

PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) in the treatment of idiopathic and inflammatory choroidal neovascularization (CNV). METHODS: This study represents a non-randomized, multicentre, interventional case series. Sixteen eyes of 16 patients with classic or predominantly classic sub- and juxtafoveal idiopathic CNV and 26 eyes of 24 patients with classic or predominantly classic sub- and juxtafoveal CNV secondary to inflammatory conditions were treated with PDT with verteporfin. Best corrected visual acuity (BCVA) before and after PDT, the number of lines gained or lost and the number of PDT sessions were analysed. RESULTS: The mean follow-up periods were 20 months (SD 11) and 16 months (SD 9) for the idiopathic and inflammatory groups, respectively. The mean BCVA in idiopathic CNV changed from 0.63 logMAR (SD 0.37) before treatment to 0.82 logMAR (SD 0.43) after treatment (p = 0.16; Student's t-test paired data). The number of treatments performed averaged 2.1 (range 1-4, SD 0.9). The mean BCVA in postinflammatory CNV changed from 0.60 logMAR (SD 0.4) before treatment to 0.57 logMAR (SD 0.6) after treatment (p = 0.79; Student's t-test paired data). The mean number of treatments was 2.6 (range 1-6, SD 1.2). CONCLUSIONS: Photodynamic therapy with verteporfin may be useful in stabilizing BCVA in patients with sub- and juxtafoveal postinflammatory CNV and subfoveal idiopathic CNV.

The pig eye as a novel model of glaucoma.

We validated the pig eye as a model of glaucoma, based on chronic elevation of intraocular pressure (IOP). IOP was elevated by cauterising three episcleral veins in each of the left eyes of five adult pigs. Right eyes were used as controls. Measurement of IOP was performed during the experiment with an applanation tonometer (Tono-Pen). Five months after episcleral vein occlusion, retinal ganglion cells (RGCs) from both cauterised and control eyes were retrogradely backfilled with Fluoro-Gold. Analysis of RGC loss and morphometric as characterization of surviving RGCs was performed using whole-mounted retinas. Elevation of IOP was apparent after three weeks of episcleral vein cauterisation and it remained elevated for at least 21 weeks (duration of the experiments). Analysis of RGC loss after chronic elevation of IOP revealed that RGC death was significant in the mid-peripheral and peripheral retina, mainly in the temporal quadrants of both retinal regions. Moreover the mean soma area of remaining RGCs was observed to increase and we found a greater loss of large RGCs in the mid-peripheral and peripheral retina. We conclude that the pattern of RGC death induced in the pig retina by episcleral vein cauterisation resembles that found in human glaucoma. On the basis of this study, the pig retina may be considered as a suitable model for glaucoma-related studies, based on its similarity with human and on its affordability.