FGF-trapping hampers cancer stem-like cells in uveal melanoma.

BACKGROUND: Cancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required. METHODS: Herein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients' clusters. RESULTS: By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes. CONCLUSIONS: Our findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM.

Incidence and management of early postoperative complications in lamellar corneal transplantation.

PURPOSE: To provide a comprehensive review of the incidence, risk factors, and management of early complications after deep anterior lamellar keratoplasty (DALK), Descemet stripping automated keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A literature review of complications, that can occur from the time of the transplant up to 1 month after the transplant procedure, was conducted. Case reports and case series were included in the review. RESULTS: Complications in the earliest postoperative days following anterior and posterior lamellar keratoplasty have shown to affect graft survival. These complications include, but are not limited to, double anterior chamber, sclerokeratitis endothelial graft detachment, acute glaucoma, fluid misdirection syndrome, donor-transmitted and recurrent infection, and Uretts-Zavalia syndrome. CONCLUSION: It is essential for surgeons and clinicians to not only be aware of these complications but also know how to manage them to minimize their impact on long-term transplant survival and visual outcomes.

Neurodevelopmental Profile in Children Affected by Ocular Albinism.

AIM: The aim of this study was to detail the neurodevelopmental profile of subjects affected by ocular albinism (OA) and to collect data on GPR143 gene analysis. DESIGN: The design of the study involves a retrospective longitudinal observational case series. METHODS: We collected data on the neurodevelopmental profile of 13 children affected by OA from clinical annual assessments conducted for a period of 6 years after the first evaluation. We described visual profile, neuromotor development and neurological examination, cognitive profile, communication and language skills and behavioral characteristics. The GPR143 gene analysis was performed as well. RESULTS: Children presented a variable combination of ocular and oculomotor disorders unchanged during the follow-up, a deficit in visual acuity and in contrast sensitivity that progressively improved. Abnormalities in pattern visual evoked potential were found. No deficits were detected at neurological examination and neuromotor development except for a mild impairment in hand-eye coordination observed in five cases. A language delay was observed in five cases, two of whom had also a developmental quotient delay at 2 years evolving to a borderline/deficit cognitive level at preschool age, difficulties in adaptive behavior and autistic-like features were found. Mutations in the GPR143 gene were identified in the two patients who presented the most severe clinical phenotype. CONCLUSION: Children with OA may share, in addition to a variable combination of ocular signs and symptoms, a neurodevelopment impairment regarding mostly the cognitive, communicative, and social area, especially those with GPR143 mutation.

Exploring the FGF/FGFR System in Ocular Tumors: New Insights and Perspectives.

Ocular tumors are a family of rare neoplasms that develop in the eye. Depending on the type of cancer, they mainly originate from cells localized within the retina, the uvea, or the vitreous. Even though current treatments (e.g., radiotherapy, transpupillary thermotherapy, cryotherapy, chemotherapy, local resection, or enucleation) achieve the control of the local tumor in the majority of treated cases, a significant percentage of patients develop metastatic disease. In recent years, new targeting therapies and immuno-therapeutic approaches have been evaluated. Nevertheless, the search for novel targets and players is eagerly required to prevent and control tumor growth and metastasis dissemination. The fibroblast growth factor (FGF)/FGF receptor (FGFR) system consists of a family of proteins involved in a variety of physiological and pathological processes, including cancer. Indeed, tumor and stroma activation of the FGF/FGFR system plays a relevant role in tumor growth, invasion, and resistance, as well as in angiogenesis and dissemination. To date, scattered pieces of literature report that FGFs and FGFRs are expressed by a significant subset of primary eye cancers, where they play relevant and pleiotropic roles. In this review, we provide an up-to-date description of the relevant roles played by the FGF/FGFR system in ocular tumors and speculate on its possible prognostic and therapeutic exploitation.

SURGICAL OUTCOMES OF VITREOMACULAR TRACTION TREATED WITH FOVEAL-SPARING PEELING OF THE INTERNAL LIMITING MEMBRANE.

PURPOSE: To compare sensitivity of the retina after complete internal limiting membrane (ILM) peeling versus foveal-sparing ILM peeling in vitrectomy for vitreomacular traction syndrome. METHODS: This was a randomized, prospective, comparative study. Thirty-four eyes were randomized to undergo peeling with foveal sparing of the ILM (FS group) or complete peeling group. Foveal and perifoveal retinal sensitivity, visual acuity, and central macular thickness were the main outcome measures. RESULTS: Parafoveal retinal sensitivity exhibited a significant improvement in both the FS and complete peeling groups (+2.43 ± 0.82 dB and +1.79 ± 0.86 dB, respectively; P = 0.037). Significant improvements were observed in both visual acuity and central macular thickness in both groups. No cases of epiretinal membrane recurrence were observed in the FS group. CONCLUSION: Both the FS and complete peeling surgical techniques are safe and yielded good anatomical and functional results; however, a significant difference in favor of FS was found in relation to the best-corrected visual acuity and perifoveal retinal sensitivity. Preservation of the foveal ILM disc allowed the anatomical restoration of the foveal architecture in most vitreomacular traction syndrome cases without signs of stiffening or ILM fibrosis over a follow-up period of 1 year.

VEGF-Independent Activation of Müller Cells by the Vitreous from Proliferative Diabetic Retinopathy Patients.

Proliferative diabetic retinopathy (PDR), a major complication of diabetes mellitus, results from an inflammation-sustained interplay among endothelial cells, neurons, and glia. Even though anti-vascular endothelial growth factor (VEGF) interventions represent the therapeutic option for PDR, they are only partially efficacious. In PDR, Müller cells undergo reactive gliosis, produce inflammatory cytokines/chemokines, and contribute to scar formation and retinal neovascularization. However, the impact of anti-VEGF interventions on Müller cell activation has not been fully elucidated. Here, we show that treatment of MIO-M1 Müller cells with vitreous obtained from PDR patients stimulates cell proliferation and motility, and activates various intracellular signaling pathways. This leads to cytokine/chemokine upregulation, a response that was not mimicked by treatment with recombinant VEGF nor inhibited by the anti-VEGF drug ranibizumab. In contrast, fibroblast growth factor-2 (FGF2) induced a significant overexpression of various cytokines/chemokines in MIO-M1 cells. In addition, the FGF receptor tyrosine kinase inhibitor BGJ398, the pan-FGF trap NSC12, the heparin-binding protein antagonist N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe Boc2, and the anti-inflammatory hydrocortisone all inhibited Müller cell activation mediated by PDR vitreous. These findings point to a role for various modulators beside VEGF in Müller cell activation and pave the way to the search for novel therapeutic strategies in PDR.

PEELING OF THE INTERNAL LIMITING MEMBRANE WITH FOVEAL SPARING FOR TREATMENT OF DEGENERATIVE LAMELLAR MACULAR HOLE.

PURPOSE: To compare the functional and anatomical results of fovea-sparing internal limiting membrane peeling during vitrectomy with those of observation for degenerative lamellar macular hole with lamellar hole-associated epiretinal proliferation. DESIGN: A prospective, randomized, comparative pilot study. METHODS: Thirty-six eyes were randomized to undergo surgery with foveal internal limiting membrane sparing (Group S) or observation only (Group C). The main outcome measures were foveal retinal sensitivity, visual acuity, and central retinal thickness. RESULTS: After 6 months, a significant difference was found in foveal retinal sensitivity between Group S (12.8 ± 1.7 dB) and Group C (9.39 ± 1.8 dB; P < 0.001). Similarly, best-corrected visual acuity improved in Group S and remained stable in Group C (respectively, 0.17 ± 0.13 and 0.46 ± 0.21 logMAR; P < 0.001). A significant increase in central retinal thickness was observed in Group S, but not in Group C (272 ± 24 vs. 147 ± 20 µm, P < 0.001). CONCLUSION: Fovea-sparing internal limiting membrane peeling is a feasible treatment for degenerative lamellar macular hole with lamellar hole-associated epiretinal proliferation, yielding better improvements in best-corrected visual acuity and foveal retinal sensitivity than observation alone. Further studies are needed to optimize this new surgical approach.

FOVEA-SPARING VERSUS COMPLETE INTERNAL LIMITING MEMBRANE PEELING IN VITRECTOMY FOR THE TREATMENT OF MACULAR HOLES.

PURPOSE: To compare the anatomical and functional outcomes of vitrectomy involving complete internal limiting membrane peeling (CP) with those of vitrectomy involving fovea-sparing internal limiting membrane peeling (FSP) for the treatment of macular holes measuring >250 µm. METHODS: This prospective, randomized, comparative study included 46 eyes with a medium or large macular hole that was randomized to undergo complete (CP group) or fovea-sparing (FSP group) internal limiting membrane peeling during vitrectomy. The main outcome measures included the foveal retinal sensitivity, visual acuity, and central retinal thickness. RESULTS: Both groups showed significantly improved foveal retinal sensitivity after surgery; the mean foveal retinal sensitivity change at 12 months after surgery was +2.8 ± 2.1 dB in the CP group and +7.2 ± 2.3 dB in the FSP group. The visual acuity also showed a significant improvement in both groups, with no significant differences in values at any time point. Regarding central retinal thickness, there was a significant decrease in the CP group and no change in the FSP group. Nicks or dimples in the inner retinal layers were visible in the fovea and perifovea of nine eyes in the CP group. CONCLUSION: Our findings suggest that both CP and FSP are safe and effective treatments leading to functional and anatomical improvements in patients with all size macular holes. However, the fovea-sparing technique may provide better functional outcomes because of a greater improvement in foveal retinal sensitivity.

Effects of an antioxidant protective topical formulation on retinal tissue of UV-exposed rabbits.

PURPOSE: The aim of this study has been to evaluate the protective effect of a topical antioxidant formulation containing riboflavin, d-α-tocopheryl polyethylene glycol (TPGS vitamin E), proline, glycine, lysine, and leucine against UV-B-induced damage in in vivo rabbit retina. METHODS: Twenty male albino rabbits were used. Animals were divided into four groups of five animals each. Control group did not receive any UV irradiation. The first group (IG) was irradiated with a UV-A lamp for 30 min; the second (IG30) and the third (IG60) groups received UV irradiation for 30 and 60 min, respectively, and were topically treated with 1 drop (approximately 50 µl) of the antioxidant formulation, every 15 min, starting 1 h before irradiation, until the end of the UC exposure. RESULTS: The retina of IG group showed extensive destruction of the retinal pigment epithelium (RPE) and of the cones and rods layer. The retina of G30 group showed a lesser destruction of both RPE and cones and rods layer. In the G60 group, retina showed an irregular thickening of the RPE, with massive edema of the inner and outer layer immediately adjacent together with a significant reduction of the photoreceptor number. CONCLUSION: Our results demonstrate that a topical application of eye drops containing riboflavin, d-α-tocopheryl polyethylene glycol (TPGS vitamin E), proline, glycine, lysine, and leucine counteracts UV retinal injury in exposed retina rabbits.

Treatment of exudative age-related macular degeneration with aflibercept combined with pranoprofen eye drops or nutraceutical support with omega-3: A randomized trial.

AIMS: The aim of this study was to determine whether a combination of intravitreal aflibercept (IVA) and pranoprofen eyedrops or nutraceutical support provides additional benefit over IVA monotherapy for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration. METHODS: This was a prospective, randomized, pilot study in 60 patients with treatment-naïve CNV. Patients were randomized 1:1:1 into three groups: aflibercept monotherapy (AM), aflibercept plus pranoprofen (AP) or aflibercept plus nutraceutical (AN) tablets containing multivitamin antioxidant and mineral supplementation plus omega-3. RESULTS: At 12 months, all groups showed significant improvement in both best-corrected visual acuity (BCVA) and central retinal thickness (CRT). The mean BCVA change from baseline to 12 months was -0.26 ± 0.06 LogMAR, -0.30 ± 0.06 LogMAR and -0.24 ± 0.04 LogMAR in the AM, AP and AN groups, respectively. The mean CRT change from baseline to 12 months was -76.9 ± 10.9 µm, -129 ± 19.9 µm and -105 ± 11.6 µm in the AM, AP and AN groups, respectively. The AN group required one less IVA injection than the AM group. CONCLUSIONS: Compared with AM, both combination groups acted synergistically, although no significant benefits in BCVA were found over AM. Nutraceutical support with omega-3 leads to a reduced need for IVA.

Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.

GOALS: The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD). BACKGROUND: About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. STUDY: CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. RESULTS: In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported. CONCLUSIONS: A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.

EPIRETINAL MEMBRANE REMOVAL WITH FOVEAL-SPARING INTERNAL LIMITING MEMBRANE PEELING: A Pilot Study.

PURPOSE: To compare the retinal sensitivity after complete internal limiting membrane (ILM) peeling with that after foveal-sparing ILM peeling during vitrectomy for Type I epiretinal membrane. METHODS: This was a prospective, randomized, comparative study. Thirty-eight eyes were randomized to undergo complete peeling of the ILM (CP group) or peeling with foveal sparing (FS group). The main outcome measures were foveal and perifoveal retinal sensitivity, visual acuity, and central retinal thickness. RESULTS: Foveal retinal sensitivity showed a significant improvement in the FS group (2.82 ± 0.85 dB, P = 0.037) versus a slight drop in the CP group (-0.66 ± 0.48 dB, P = 1). Perifoveal retinal sensitivity slightly improved in both groups (0.47 ± 0.37 dB, P = 1 in the CP group and 0.79 ± 0.42 dB, P = 0.77 in the FS group), showing a similar trend without significant differences. Significant improvements were observed in both visual acuity and central retinal thickness in both groups. However, three cases in the FS group showed epiretinal membrane recurrence and required revision surgery with complete ILM removal. CONCLUSION: Internal limiting membrane peeling may reduce retinal sensitivity and significantly increase the incidence of microscotomas. However, the higher epiretinal membrane recurrence rate after the foveal-sparing technique limits the effectiveness of this procedure. Further studies must be conducted to determine if it is safe to leave a portion of the ILM in front of the fovea.

Heavy and standard silicone oil: intraocular inflammation.

PURPOSE: Proliferative vitreoretinopathy in the inferior retina remains clinically challenging. Heavier-than-water intraocular tamponades have been developed to improve inferior tamponading properties, and their chemical compositions have been substantially improved over the years, in parallel with developments in vitrectomy instrumentation and surgical techniques. Herein we present an updated review of the clinical use of standard formulations and HSO, focusing on analysis of the intraocular inflammation associated with endotamponade agents, and comparison of the adverse effects of these agents on the physical and biological properties of the eye. METHODS: A detailed literature search was conducted on PubMed, EMBASE, Cochrane Library, and Google Scholar using the key words. Fifty-eight articles matched our inclusion criteria that were included in this systematic review. RESULTS: Perfluorocarbon liquids and partially fluorinated alkanes are associated with tamponade emulsification, intraocular inflammation, and rises in intraocular pressure, but these associations are not as strong when these substances are mixed with a heavy silicone oil (HSO). Two recently approved heavy silicone oil tamponades, Oxane HD and Densiron 68, are now available for use in clinical practice. While the complication spectrum of the new generation of these HSOs seems to be similar to that of conventional silicone oil tamponades, they provide better support for the inferior retina and the posterior pole. CONCLUSION: Both regular and heavy silicone oils usually yield good success rates in cases of complicated retinal detachment. Decisions as to whether to utilize heavy or regular silicone oil should be made on a case-by-case basis.

Inflammation and N-formyl peptide receptors mediate the angiogenic activity of human vitreous humour in proliferative diabetic retinopathy.

AIMS/HYPOTHESIS: Angiogenesis and inflammation characterise proliferative diabetic retinopathy (PDR), a major complication of diabetes mellitus. However, the impact of inflammation on the pathogenesis of PDR neovascularisation has not been elucidated. Here, we assessed the capacity of PDR vitreous fluid to induce pro-angiogenic/proinflammatory responses in endothelium and the contribution of the inflammation-related pattern recognition N-formyl peptide receptors (FPRs) in mediating these responses. METHODS: Pooled and individual pars plana vitrectomy-derived PDR vitreous fluid ('PDR vitreous') samples were assessed in endothelial cell proliferation, motility, sprouting and morphogenesis assays, and for the capacity to induce proinflammatory transcription factor activation, reactive oxygen species production, intercellular junction disruption and leucocyte-adhesion molecule upregulation in these cells. In vivo, the pro-angiogenic/proinflammatory activity of PDR vitreous was tested in murine Matrigel plug and chick embryo chorioallantoic membrane (CAM) assays. Finally, the FPR inhibitors Boc-Phe-Leu-Phe-Leu-Phe (Boc-FLFLF) and Ac-L-Arg-Aib-L-Arg-L-Cα(Me)Phe-NH2 tetrapeptide (UPARANT) were evaluated for their capacity to affect the biological responses elicited by PDR vitreous. RESULTS: PDR vitreous activates a pro-angiogenic/proinflammatory phenotype in endothelial cells. Accordingly, PDR vitreous triggers a potent angiogenic/inflammatory response in vivo. Notably, the different capacity of individual PDR vitreous samples to induce neovessel formation in the CAM correlates with their ability to recruit infiltrating CD45+ cells. Finally, the FPR inhibitor Boc-FLFLF and the novel FPR antagonist UPARANT inhibit neovessel formation and inflammatory responses triggered by PDR vitreous in the CAM assay. CONCLUSIONS/INTERPRETATION: This study provides evidence that inflammation mediates the angiogenic activity of PDR vitreous and paves the way for the development of FPR-targeting anti-inflammatory/anti-angiogenic approaches for PDR therapy.

Zebrafish (Danio rerio) embryo as a platform for the identification of novel angiogenesis inhibitors of retinal vascular diseases.

Pathological angiogenesis of the retina is a main cause of blindness. Therapeutic approaches targeting vascular endothelial growth factor, a main angiogenesis inducer in retinal vascular diseases, show significant limitations. Thus, experimental models of retinal neovascularization remain crucial for investigating novel anti-angiogenic strategies and bringing them to patients. Recent observations have shown that eye neovascularization in zebrafish (Danio rerio) embryo may represent a novel target for the identification of angiogenesis inhibitors. This review highlights the use of zebrafish embryo as an innovative model system for the screening of anti-angiogenic molecules to be employed for the treatment of angiogenesis-dependent eye diseases.

3D endothelial cell spheroid/human vitreous humor assay for the characterization of anti-angiogenic inhibitors for the treatment of proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) represents a main cause of acquired blindness. Despite the recognition of the key role exerted by vascular endothelial growth factor (VEGF) in the pathogenesis of PDR, limitations to anti-VEGF therapies do exist. Thus, rapid and cost-effective angiogenesis assays are crucial for the screening of anti-angiogenic drug candidates for PDR therapy. In this context, evaluation of the angiogenic potential of PDR vitreous fluid may represent a valuable tool for preclinical assessment of angiostatic molecules. Here, vitreous fluid obtained from PDR patients after pars plana vitrectomy was used as a pro-angiogenic stimulus in a 3D endothelial cell spheroid/human vitreous assay. The results show that PDR vitreous is able to stimulate the sprouting of fibrin-embedded HUVEC spheroids in a time- and dose-dependent manner. A remarkable variability was observed among 40 individual vitreous fluid samples in terms of sprouting-inducing activity that was related, at least in part, to defined clinical features of the PDR patient. This activity was hampered by various extracellular and intracellular signaling pathway inhibitors, including the VEGF antagonist ranibizumab. When tested on 20 individual vitreous fluid samples, the inhibitory activity of ranibizumab ranged between 0 and 100% of the activity measured in the absence of the drug, reflecting a variable contribution of angiogenic mediators distinct from VEGF. In conclusion, the 3D endothelial cell spheroid/human vitreous assay represents a rapid and cost-effective experimental procedure suitable for the evaluation of the anti-angiogenic activity of novel extracellular and intracellular drug candidates, with possible implications for the therapy of PDR.

Spectral-domain optical coherence tomography findings in idiopathic lamellar macular hole.

BACKGROUND: To evaluate demographic, functional, and morphological parameters of idiopathic lamellar macular hole (ILMH). METHODS: Observational longitudinal retrospective study. Optical coherence tomography examinations and corresponding clinical charts of a series of consecutive patients affected by ILMH, between January 2010 and March 2015, from the database of the Department of Ophthalmology of Trento Hospital, Italy, have been collected and examined. Demographic and functional parameters were: age (year), gender (male/female), eye (right/left), lens status, best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (LogMAR). Tomographic parameters were: LMH shape pattern (intraretinal splitting LMH, IR split LMH, and V-shaped LMH, V LMH), posterior vitreous detachment (PVD yes/ PVD no), ERM type (conventional ERM and atypical ERM), integrity of ellipsoid zone (EZ) and external limiting membrane (ELM), residual foveal thickness (RFT) micron (µ), maximal diameter of intraretinal splitting (MDIRS) (µ). RESULTS: One hundred and eighty-nine eyes of 175 patients were included. The mean age was 72.84 ± 9.6, range 41-96 years. BCVA mean was 0.24 ± 0.25, range 0 -1.3 LogMAR. One hundred and forty-one eyes (74.6 %) were affected by IR split LMH, 48 eyes (25.4 %) were affected by V LMH. Every cases of ILMH were associated with ERM: 117 (61.9 %) conventional ERM, 72 (38.1 %) atypical ERM. A significant prevalence of female gender, phakic condition, and PVD in conventional ERM ILMH subgroup (P = 0.000) was found. BCVA mean was better in the conventional ERM ILMH subgroup (P = 0.000). An association between the interruption of the outer retinal layers (EZ and ELM) and atypical ERM ILMH subgroup was highlighted (P = 0.000). The statistical analysis showed a correlation between BCVA and integrity of ELM (P = 0.000). RFT significantly decreased in atypical ERM ILMH subgroup at 24 months compared to time point 0 (P = 0.027). A progressive increase of MDIRS in both subgroups at 12 months and in atypical ERM ILMH subgroup at 24 months (P = 0.007) was highlighted. CONCLUSIONS: This study demonstrated that ILMH was not a stable condition, showing morphological changes and an involvement of the outer retinal layers during the 2 years of follow-up.

Comparison of half-dose photodynamic therapy and 689 nm laser treatment in eyes with chronic central serous chorioretinopathy.

PURPOSE: To compare visual and anatomical outcomes between half-dose photodynamic therapy (hd-PDT) and 689 nm laser therapy (689-LT) in chronic central serous chorioretinopathy (CSC). METHODS: Forty eyes of 40 patients with symptomatic chronic CSC were randomized in a 1:1 ratio to receive either hd-PDT or 689-LT delivering 95 J/cm2 via an intensity application of 805 mW/cm2 over 118 s. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography findings were compared between the two treatment groups. RESULTS: Mean CSC duration was 17.1 ± 6.66 weeks and 18.7 ± 7.46 weeks in the hd-PDT and 689-LT groups respectively. Both groups showed significant BCVA improvements, as well as reductions in central retinal and subfoveal choroidal thickness. Although hd-PDT led to a faster reduction in central retinal thickness, no significant differences were recorded between groups for any other measured parameter at any time point. Complete photoreceptor recovery was observed in eight and seven eyes in the hd-PDT and 689-LT groups respectively. CONCLUSIONS: Both hd-PDT and 689-LT were effective at treating chronic CSC. Further studies are warranted to evaluate long-term safety and efficacy.

Relationship between different subpopulations of circulating CD4+ T lymphocytes and microvascular or systemic oxidative stress in humans.

BACKGROUND AND OBJECTIVE: Different components of the immune system, including innate and adaptive immunity (T effector lymphocytes and T regulatory lymphocytes - TREGs) may be involved in the development of hypertension, vascular injury and inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular oxidative stress. Our objective was to investigate possible relationships between T-lymphocyte subtypes and systemic and microvascular oxidative stress in a population of normotensive subjects and hypertensive patients. PATIENTS AND METHODS: In the present study we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. A peripheral blood sample was obtained before surgery for assessment of T lymphocyte subpopulations by flow cytometry and circulating indices of oxidative stress. RESULTS: A significant direct correlation was observed between Th1 lymphocytes and reactive oxygen species (ROS) production (mainly in microvessels). Additionally, significant inverse correlations were observed between ROS and total TREGs, or TREGs subtypes. Significant correlations were detected between circulating indices of oxidative stress/inflammation and indices of microvascular morphology/Th1 and Th17 lymphocytes. In addition, a significant inverse correlation was detected between TREGs in subcutaneous small vessels and C reactive protein. CONCLUSIONS: Our data suggest that TREG lymphocytes may be protective against microvascular damage, probably because of their anti-oxidant properties, while Th1-Th17 lymphocytes seem to exert an opposite effect, confirming an involvement of adaptive immune system in microvascular damage.

Assessment of a smartphone-based camera for fundus imaging in animals.

OBJECTIVE: To assess the use of an optical device (D-EYE; Si14 S.p.A.) attached to a modern smartphone (iPhone 5; Apple Inc.) for imaging the fundus in small animals. ANIMALS STUDIED: Five dogs, five cats, and five rabbits with clear media were imaged using a prototype of the D-EYE. PROCEDURE: The optical device was composed of lenses, polarizing filters, a beam splitter, a diaphragm, and mirrors, attached to a smartphone via a metal shell. Images were obtained 20 min after pupil dilation with topical 0.5% tropicamide in a darkened room, to ensure maximum pupillary dilation. Focus was set to the infinite when the autofocus was overwhelmed. Light intensity was adapted to each animal via the application (minimum light intensity for imaging the tapetal region, maximum light intensity for imaging the nontapetal region). Both still images and video sequences were recorded for each animal. RESULTS: Posterior segment structures were visible in all animals: optic nerve head, tapetum lucidum (when present), nontapetal region, retinal vessels, and choroidal vessels (when the retinal pigment epithelium and the choroidal pigmentation were discreet). Focal light artifacts were common when photographing the tapetum lucidum. Recording videos allowed the visualization of dynamic phenomena. CONCLUSIONS: The D-EYE assessed appears to be an easy means of obtaining images of the posterior segment structures.