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Purpose: This study evaluates if the addition of a curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC; Diabec®, Alfa Intes, Italy) to intravitreal injections of dexamethasone (DEX-IVT) can affect the morphological retinal characteristics, extending the steroid re-treatment period in patients with diabetic macular edema (DME).Methods: A randomized controlled clinical trial was carried out in DME patients, randomly assigned to receive DEX-IVT or DEX-IVT and a CHC. The evaluation of the mean difference of central retinal thickness (CRT) was the primary aim. Secondary aims were the evaluations of best-corrected visual acuity, differences in the predetermined retinal layer thickness, the number/time of re-treatment, and the assessment of safety.Results: A total of 73 DME patients were included (35 in the control group and 38 in the combined therapy group). In both the control and combined therapy groups, the mean CRT change from T0 to the 6 months’ evaluation was significant (p = 0.00). The mean CRT result was significantly different at month 4 (p = 0.01) between the control and combined therapy groups, with a greater reduction in the combined therapy group, in particular, in patients with ≤10 years of diabetes. A trend of CRT reduction in the combined therapy group has been observed also considering patients with subfoveal neuroretinal detachment. In addition, we observed that the reduction of inner retinal layer thickness was greater in the combination group, in comparison with controls.Conclusion: The combination of a CHC to DEX-IVT is a promising therapeutic option in case of DME, in particular, for patients with early-stage diabetes and with an inflammatory phenotype. Further studies will be necessary to confirm these findings.

Objective To report the results of a global survey on cataract practice patterns related to preoperative, intraoperative and postoperative care, surgical setting and personnel allocation.Methods and analysis An online 28 questions survey was sent to 240 ophthalmologists asking to describe prevailing trends in their institutions across 38 countries and 5 continents. Questions inquired country, institution, surgical volume and setting, anaesthesia, preoperative and intraoperative examination and postsurgical care. Statistical analysis used crosstabs lambda statistics for non-parametric nominal variables. P value less than 0.05 was considered statistically significant.Results 209/240 (87%) ophthalmologists responded: 38% representing public hospitals, 36% private practices and 26% academic sites; overall surgical volume was between 241 700 and 410 500 cataracts per year. There was a significant correlation between type of institution and surgical volume. Complete results available in online (https://freeonlinesurveys.com/r/W6BcLLxy).Conclusion Cataract surgery related patterns of perioperative care showed significant difference among respondents, regardless to type of institution, surgical volume and country. Many evidence-based procedures are unevenly practiced around the world and some widespread and expensive habits lack solid scientific evidence while consuming enormous amount of resources both monetary and human. There is a need to reach consensus and share evidence-based practice patterns.

PurposeTo introduce a novel method to quantitively analyse in three dimensions traction forces in a vast area of the ocular posterior pole.MethodsRetrospective analysis of 14 eyes who underwent peeling surgery for idiopathic, symptomatic and progressive epiretinal membrane. The technique measures the shift in position of vascular crossings after surgery from a fixed point, which is the retinal pigmented epithelium. This shift is defined as the relaxation index (RI) and represents a measure of the postoperative movement of the retina due to released traction after surgery.ResultsBest-corrected visual acuity was significantly better than baseline at all follow ups while the RI had its maximum value at baseline. Moreover, we found a significant correlation between best-corrected visual acuity at 6 months and RI at baseline.ConclusionWhile all previous published methods focused on bi-dimensional changes observed in a small region, this study introduces a three-dimensional assessment of tractional forces. Future integration of RI into built-in processing software will allow systematic three-dimensional measurement of intraretinal traction.

AIM: To describe the morphological changes of the lamina cribrosa (LC) in patients with optic nerve compression. METHODS: Cross-sectional study. Twenty eyes with optic nerve compression, affected by Graves' ophthalmopathy (GO) were compared with 18 refractive error-matched healthy eyes. The following examinations were performed: best-corrected visual acuity (BCVA), intraocular pressure, optic nerve echography, visual field, SD-OCT including the retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and LC thickness and extent. RESULTS: A-scan revealed significant differences in the subarachnoid space (SAS) between the affected and control groups. LC thickness and LC area were 233 µm (SD 23) and 0.41 mm2 (SD 0.19), respectively. Average GCC thickness (P=0.0005), LC thickness (P=0.001), MD (P=0.001) and PSD (P=0.001) differed significantly between the two groups; whereas LC area (P=0.2) and average RFNL (P=0.1) did not. CONCLUSION: Optic nerve compression reduces the SAS thereby altering the morphology of LC thickness and causing GCC damage.

Lamellar macular holes (LMHs) may show morphological and functional deterioration over time, yet no definite prognostic factor for progression has been identified. Since neurovascular retinal unit impairment may take part in neurodegeneration, we compare progressive LMHs to stable ones in optical coherence tomography (OCT) angiography parameters. Methods: OCT B scans of eyes with LMH were analyzed to detect the presence of tissue loss (TL) over time, allowing us to identify a TL group and a stable (ST) group (14 patients each). The best corrected visual acuity (BCVA) at each considered imaging time point was collected. Lastly, patients underwent macular OCT angiography. Results: BCVA at last follow up was significantly reduced in the TL group compared to both the ST group and TL group baseline assessment. SCP foveal vessel density (VD), SCP and deep capillary plexus (DCP) perfusion density (PD) and parafoveal PD were lower in the TL group. Linear correlations between quantitative TL over time and parafoveal PD in SCP and between the speed of TL and BCVA variation during follow up were also detected. Conclusions: TL in LMHs is associated with both OCT angiography modifications and BCVA deterioration over time. We suggest these findings to be a manifestation of foveal Muller cell impairment in progressive LMHs.

Letter to the Editor

INTRODUCTION:Epiretinal traction is not responsible only for epiretinal but also intraretinal changes. This study aims to describe structural and vascular intraretinal changes after macular peeling in idiopathic (iERM) vs diabetic ERM (dERM). METHODS:We conducted a prospective interventional study on forty-two eyes, 23 with iERMs and 19 with dERMs, undergoing ERM-ILM peeling. We performed SD-OCT preoperatively, 1 and 6 months postoperatively to assess central macular thickness (CMT), intraretinal cysts (IC) and/or continuous ectopic inner foveal layers (CEIFL), superficial and deep capillary free zone (CFZ) area on OCT-A. Glial fibrillary acidic protein (GFAP), as a Müller cells marker, was detected immunohistochemically on ILM specimens, to assess Müller cells iatrogenic damage. RESULTS:The CEIFLs were significantly more common in iERMs (12 (52.2%) in iERMs vs 2 (10.5%) in dERMs, p = 0.004), whereas ICs in dERMs (6 (26.1%) in iERMs vs 17 (89.5%) in dERMs, p

To highlight the differences in macular pigment optical density (MPOD) between eyes with vitreoretinal interface syndrome and healthy control eyes, to assess the changes in MPOD in eyes treated with macular peeling, to investigate the relationships between MPOD changes and measures of retinal sensitivity such as best corrected visual acuity (BCVA) and microperimetry.In this cross-sectional comparative study, 30 eyes affected by idiopathic epiretinal membrane (iERM, 15eyes) or full-thickness macular hole (FTMH, 15eyes) were compared with 60 eyes from 30 healthy age-matched patients. MPOD values (mean MPOD, maximum MPOD, MPOD area, and MPOD volume) were measured in a range of 4°-7° of eccentricity around the fovea, using the one-wavelength reflectometry method (Visucam 200, Carl-Zeiss Meditec). Patients affected by iERM and FTMH were treated with vitrectomy and epiretinal membrane-inner limiting membrane (ERM-ILM) peeling, with follow-up examinations performed preoperatively and 6 months postoperatively. The main outcome measures were the differences in MPOD between eyes with vitreoretinal interface syndrome and healthy eyes, changes in MPOD after ERM-ILM peeling, and relationships between MPOD and functional changes.Mean MPOD differed significantly between control eyes and those with iERM (P = .0001) or FTMH (P = .0006). The max MPOD and MPOD area increased, but not significantly. After peeling, the only significant change in MPOD was in MPOD volume (P = .01). In the ERM group, postoperative mean MPOD correlated significantly with best-corrected visual acuity (r = .739, P = .002).MPOD was reduced in patients with iERM or FTMH compared with healthy eyes. We found a significant correlation between the mean postoperative MPOD and postoperative BCVA, hypothesizing that the postoperative increase in mean MPOD could be due to a change in distribution for unfolding and expansion of the fovea after the peeling. MOPD may be considered as a prognostic factor associated with a good visual prognosis in patients with iERM.

INTRODUCTION:Elements such as zinc, iron, copper, sulphur and phosphorus have been identified in retinal layers and implicated in vital retinal functions. Regarding mineral composition of epiretinal membranes (ERMs), literature is lacking. This study aimed to analyze both mineral composition and anatomical ultrastructure of ERMs to clarify the pathophysiology of this disease. METHODS:Twenty ERMs (10 diabetic ERMs and 10 idiopathic ERMs) from 20 patients were harvested during pars plana vitrectomy. Scanning Electron Microscopy (SEM) was used to investigate the anatomical ultrastructure of the peeled ERMs. Mineral composition was analyzed using energy-dispersive spectrometry (EDS). The most frequent elements were evaluated in relation to appearance of ERMs analyzed at SEM and at OCT images. RESULTS:Sulphur was the most frequent element found (in 80% of the samples), followed by sodium (50%) and phosphorus (45%). The presence of these elements was not significantly different between diabetic and idiopathic ERMs (P >0.05). Using SEM we found a folded tissue in all ERMs, except in 4 ERMs, where we observed only a smooth tissue. There was a trend of sodium to be more frequent in ERMs with folded layers at SEM examination. CONCLUSIONS:Several elements were identified in ERMs, and sulphur, sodium and phosphorus were the most frequent ones. This finding may help to understand their role in the physiopatology of epiretinal proliferation and in glial activation.

[This corrects the article DOI: 10.1371/journal.pone.0197065.].

Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti-thrombophilic effects due to FXIII-A G185T variant and photo-thrombotic action of PDT-V toward CNV provides several clues about the rationale of this intriguing pharmacogenetic correlation. Further investigations are warranted to outline the appropriate paradigm for guiding PDT-V utilization in the course of the combined therapeutic protocol for neovascular macular degeneration.

Aim: The intraocular silicone oil (SO) tamponades used in the treatment of retinal detachment (RD) have been associated with a difference ocular hypertension (OH) rate. To clarify, if this complication was associated to use of standard SO (SSO) versus heavy SO (HSO), we performed a systematic review and meta-analysis of comparative study between two kind of SO (standard or light vs. heavy) for the treatment of RD and macular hole, without restriction to study design. Materials and Methods: The methodological quality of two randomized clinical trials (RCTs) were evaluated using the criteria given in the Cochrane Handbook for Systematic Reviews of Intervention, while three non-RCTs were assessed with the Newcastle-Ottawa Scale and Strengthening the Reporting of Observational Studies in Epidemiology checklists. We calculated Mantel-Haenszel risk ratio (RR) with 95% confidence intervals (95% CIs). The primary outcome was the rate of patients with OH treated with SSO compared to HSO. Results: There were a higher number of rates of OH in HSO compared to SSO. This difference was statistically significant with the fixed effect model (Mantel-Haenszel RR; 1.55; 95% CI, 1.06-2.28; P = 0.02) while there was not significative difference with the random effect model (Mantel-Haenszel RR; 1.51; 95% CI, 0.98-2.33; P = 0.06). Conclusion: We noted a trend that points out a higher OH rate in HSO group compared to SSO, but this finding, due to the small size and variable design of studies, needs to be confirmed in well-designed and large size RCTs.

[This corrects the article DOI: 10.1371/journal.pone.0174297.].

Aims : To report a prospective non-comparative consecutive interventional study on the safety and efficacy of 23-Gauge transconjunctival sutureless pars plana vitrectomy for primary rhegmatogenous retinal detachment (RRD). Materials and Methods: Fifty eyes of 50 consecutive patients were recruited between June 2007 and January 2008. All surgeries were performed using the one-step 23-Gauge system with angled incisions. The surgical protocol consisted of a minimum of eight clinical visits: baseline, 1 day, 1 week, 1-, 3- and 6- months after the initial surgery. The endpoints were anatomical, functional results and complications arising from the surgery. Results : Anatomical success was achieved in 82% of cases (41 out of 50) with single surgery and rose to 98% (49 out of 50) with additional surgery. Mean visual acuity improved from logMAR 0.48(SD 0.36) to 0.26(SD 0.31), P < 0.001. Two cases with ocular hypotony, defined as an intraocular pressure ≤ 6mmHg, that were associated with a choroidal detachment were seen. Conclusions : Acceptable anatomical and functional success rates can be achieved with primary 23-Gauge transconjunctival sutureless vitrectomy for RRD. We found that the approach technique is different from conventional vitrectomy and the complications arising from post surgical hypotony and leakage from sclerotomies are potentially higher compared to 20-Gauge vitrectomy.

Aim: The aim was to evaluate the safety and efficacy of the "cross-cylinder" technique in the correction of astigmatism. Setting and Design: A prospective interventional study from a university eye department was conducted. Material and Methods: The photoastigmatic refractive keratectomy (PARK) using the "cross-cylinder" technique was performed in 102 eyes of 84 patients with at least 0.75 D of astigmatism. The study population was divided into two groups: in the first group the preoperative astigmatic power ranged from −0.75 D to −3.00 D (group 1), in the second group it ranged from −3.25 D to −6.00 D (group 2). Group 1 included 82 eyes of 67 patients (29 males and 38 females) with a mean cylinder power of −1.90 ± 0.63 D, group 2 included 20 eyes of 17 patients (13 males and 4 females) with a mean cylinder power of -4.28 ± 0.76 D. All eyes were targeted for emmetropia. The results were evaluated using Calossi′s vector analysis method. Six-month postoperative outcomes are presented. Results: Six months after PARK the mean sphere for the entire cohort was +0.28 ± 0.75 D (range +2.5 to −2 D), the mean cylindrical power was +0.33 ± 0.51 D (range +2.5 to −1.25 D) and the mean spherical equivalent refraction was +0.73 ± 0.81 D (range +1.75 to −2 D). Conclusions: The cross-cylinder technique may be safely used with predictable results for the correction of astigmatism.

Aims: To compare the quality of vision in pseudophakic patients implanted with aspherical and spherical intraocular lenses (IOLs). Materials and Methods: Randomized prospective longitudinal intrapatient comparison between aspherical and spherical IOLs performed on 22 patients who underwent bilateral cataract surgery. Best corrected visual acuity, subjective contrast sensitivity, Strehl ratio and spherical aberrations (SA), and higher order wavefront aberrations for a 3.5 mm and a 6.0 mm pupil were measured after 3 months of cataract surgery. Results: SA (Z4,0) decreased significantly in eyes with aspherical IOL implant (P = 0.004). Modulation transfer function (MTF) and point spread function (PSF) resulted no significant difference between the two groups (P = 0.87; P = 0.32). Conclusion: Although the SA is significantly lower in eyes implanted with aspherical IOL, the quality of vision determined with MTF and PSF does not significantly differ for subjective and objective parameters that were analyzed.

Mario R Romano1, Ugo Cipollone2, Francesco Semeraro3, Michele Rinaldi4, Ciro Costagliola11Dipartimento di Scienze per la Salute, Università degli Studi del Molise, Campobasso; 2Dipartimento di Oftalmologia, Ospedale G Vietri, Larino, Campobasso; 3Clinica Oculistica, Università degli Studi di Brescia, Brescia; 4Clinica Oculistica, II Università degli Studi di Napoli, Napoli, ItalyObjective: To report the efficacy and safety of combined photodynamic therapy (PDT) and intravitreal bevacizumab (IVB) injection in the treatment of idiopathic polypoidal choroidal vasculopathy (IPCV).Material and methods: A prospective case series of 10 eyes of 10 consecutive patients affected by IPCV with subfoveal involvement. PDT plus IVB (1.25 mg/0.05 mL) injection two weeks later was performed in all patients. Two adjunctive injections of bevacizumab were scheduled at four and eight weeks after the initial treatment. Best-corrected visual acuity (BCVA), fluorescein and indocyanine green angiographies, and optical coherence tomography were obtained at baseline, and at one, three, six, nine, and 12 months.Results: The combined treatment led to an improvement of both neurosensory detachment and pigmented epithelial detachment in all eyes, with a decrease of exudation and regression of macular thickness, which remained stable to the end of follow-up. However, BCVA remained stable over the 12 months of follow-up.Conclusion: These findings demonstrate that PDT/IVB combined therapy is able to achieve morphologic stabilization of the IPCV lesion, through a rapid decrease of macular thickness and regression of the size of polypoidal vascular lesion.Keywords: combined treatment, idiopathic polypoidal choroidal vasculopathy, age-related macular degeneration, intravitreal bevacizumab, photodynamic therapy

Subretinal injection is performed in vitreoretinal surgery with two main aims, namely, the subretinal delivery of therapeutic agents and subretinal injection of fluid to induce a controlled and localized macular detachment. The growing interest in this technique is mainly related to its suitability to deliver gene therapy in direct contact with target tissues. However, subretinal injection has been also used for the surgical management of submacular hemorrhage through the subretinal delivery of tissue plasminogen activator, and for the repair of full-thickness macular holes, in particular refractory ones. In the light of the increasing importance of this maneuver in vitreoretinal surgery as well as of the lack of a standardized surgical approach, we conducted a comprehensive overview on the current indications for subretinal injection, surgical technique with the available variations, and the potential complications.

Inherited macular dystrophies refer to a group of degenerative conditions that predominantly affect the macula in the spectrum of inherited retinal dystrophies. Recent trends indicate a clear need for genetic assessment services in tertiary referral hospitals. However, establishing such a service can be a complex task due to the diverse skills required and multiple professionals involved. This review aims to provide comprehensive guidelines to enhance the genetic characterization of patients and improve counselling efficacy by combining updated literature with our own experiences. Through this review, we hope to contribute to the establishment of state-of-the-art genetic counselling services for inherited macular dystrophies.

Age related macular degeneration (AMD) and diabetic retinopathy (DR) are multifactorial, neurodegenerative and inflammatory diseases of the eye primarily involving cellular and molecular components of the outer and inner blood-retina barriers (BRB), respectively. Largely contributed by genetic factors, particularly polymorphisms in complement genes, AMD is a paradigm of retinal immune dysregulation. DR, a major complication of diabetes mellitus, typically presents with increased vascular permeability and occlusion of the retinal vasculature that leads, in the proliferative form of the disease, to neovascularization, a pathogenic trait shared with advanced AMD. In spite of distinct etiology and clinical manifestations, both pathologies share common drivers, such as chronic inflammation, either of immune (in AMD) or metabolic (in DR) origin, which initiates and propagates degeneration of the neural retina, yet the underlying mechanisms are still unclear. As a soluble pattern recognition molecule with complement regulatory functions and a marker of vascular damage, long pentraxin 3 (PTX3) is emerging as a novel player in ocular homeostasis and a potential pharmacological target in neurodegenerative disorders of the retina. Physiologically present in the human eye and induced in inflammatory conditions, this protein is strategically positioned at the BRB interface, where it acts as a “molecular trap” for complement, and modulates inflammation both in homeostatic and pathological conditions. Here, we discuss current viewpoints on PTX3 and retinal diseases, with a focus on AMD and DR, the roles therein proposed for this pentraxin, and their implications for the development of new therapeutic strategies.

Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.

Abstract Background 27-gauge (27G) and 25-gauge (25G) transconjunctival sutureless vitrectomy (TSV) were considered equal about safety, effectiveness and vitrectomy time for the treatment of rhegmatogenous retinal detachment (RRD), although larger and long-term comparative studies are needed to confirm previous knowledge. Furthermore, a combined comparison of time duration of surgery and vitreous removal was never performed. Our purpose was to compare the safety and efficacy of 27G versus 25G TSV for the treatment of uncomplicated RRD over a 1-year follow-up. Methods A 12-months single-center prospective, randomized, interventional study of 92 consecutive patients was performed. 46 patients underwent 27G TSV (Group 1) and 46 underwent 25G TSV (Group 2). Primary outcomes were primary and final reattachment rate, and final functional success (visual acuity ≥ 20/200, 1 LogMar). Secondary outcomes were the surgical and vitrectomy time. Complications were recorded. Results All functional and morphologic data at baseline and at all follow-up time points up to 12 months after surgery were available for only 88 patients. Four patients in Group 1 dropped out of the study after surgery. There was no significant difference in baseline characteristics between the two groups. Primary and final reattachment rates were 90.5% and 100% in Group 1, and 95.6% and 100% in Group 2, respectively (p > .05, p > .05, respectively). Visual acuity improved from 1.5 ± 1.09 LogMar to 0.38 ± 0.55 LogMar in Group 1 (p .05). The surgical time was 73.2 ± 11.3 min with 27G TSV and 64.4 ± 9.5 min with 25G TSV (p = .0001). The vitrectomy time was 19.9 ± 3.8 min with 27G TSV and 20.8 ± 3.8 min with 25G TSV (p > .05). One single case of choroidal detachment occurred. Conclusions Reattachment rates, functional success and vitrectomy time were comparable between 27G and 25G TSV for RRD. Surgical time was significantly longer using 27G vitrectomy.

Abstract Purpose To describe swept-source optical coherence tomography and optical coherence tomography angiography retinal changes in a case of acute toxoplasmic chorioretinitis both at the time of diagnosis and after healing. Case presentation A 57-year-old white woman suffering from acquired toxoplasmic chorioretinitis underwent swept-source optical coherence tomography and optical coherence tomography angiography both at the time of diagnosis and after healing. In the acute phase of the disease, swept-source optical coherence tomography clearly showed retinal and choroidal involvement in the superficial retina and in the choroidal swelling. Optical coherence tomography angiography showed a complete loss of deep and superficial capillary networks and of choroidal vessels in the area of the inflammation. After healing, swept-source optical coherence tomography showed a retinal thinning of the area involved, with a subversion of retinal layers and no visible change at the choroid level. On the other hand, optical coherence tomography angiography showed the persistence of a vascular occlusion at the retina and choroid level. Conclusion This is the first case in the optical coherence tomography angiography literature that shows the imaging of toxoplasmic chorioretinal lesions. This case confirms the involvement of the retina and choroid in toxoplasmic uveitis and the disruptive potential of such inflammation. The optical coherence tomography angiography performed after healing showed a persistent ablation of the retina, choriocapillaris, and choroidal vessels. The non-invasive optical coherence tomography angiography imaging technique may have diagnostic and prognostic value in regard to toxoplasmic uveitis.

Recent evidence in basic science is leading to a growing interest in the possible role of curcumin in treating retinal diseases. Curcumin has been demonstrated to be able to modulate gene transcription and reduce ganglion cell apoptosis, downgrade VEGF, modulate glucose levels and decrease vascular dysfunction. So far, the use of curcumin has been limited by poor bioavailability; to overcome this issue, different types of carriers have been used. Multiple recent studies disclosed the efficacy of using curcumin in treating different retinal conditions. The aim of this review is to comprehensively review and discuss the role of curcumin in retinal diseases from bench to bedside.

Dysregulation of the complement system is central to age-related macular degeneration (AMD), the leading cause of blindness in the developed world. Most of the genetic variation associated with AMD resides in complement genes, with the greatest risk associated with polymorphisms in the complement factor H (CFH) gene; factor H (FH) is the major inhibitor of the alternative pathway (AP) of complement that specifically targets C3b and the AP C3 convertase. Long pentraxin 3 (PTX3) is a soluble pattern recognition molecule that has been proposed to inhibit AP activation via recruitment of FH. Although present in the human retina, if and how PTX3 plays a role in AMD is still unclear. In this work we demonstrated the presence of PTX3 in the human vitreous and studied the PTX3-FH-C3b crosstalk and its effects on complement activation in a model of retinal pigment epithelium (RPE). RPE cells cultured in inflammatory AMD-like conditions overexpressed the PTX3 protein, and up-regulated AP activating genes. PTX3 bound RPE cells in a physiological setting, however this interaction was reduced in inflammatory conditions, whereby PTX3 had no complement-inhibiting activity on inflamed RPE. However, on non-cellular surfaces, PTX3 formed a stable ternary complex with FH and C3b that acted as a “hot spot” for complement inhibition. Our findings suggest a protective role for PTX3 in response to complement dysregulation in AMD and point to a novel mechanism of complement regulation by this pentraxin with potential implications in pathology and pharmacology of AMD.

The retinal pigmented epithelium (RPE) plays a pivotal role in retinal homeostasis. It is therefore an interesting target to fill the unmet medical need of different retinal diseases, including age-related macular degeneration and Stargardt disease. RPE replacement therapy may use different cellular sources: induced pluripotent stem cells or embryonic stem cells. Cells can be transferred as suspension on a patch with different surgical approaches. Results are promising although based on very limited samples. In this review, we summarize the current progress of RPE replacement and provide a comparative assessment of different published approaches which may become standard of care in the future.

Toxic tumour syndrome (TTS) is a particularly aggressive form of secondary vasculopathy occurring after radiation therapy of uveal melanoma due to the persistence of the necrotic tumour mass inside the eye. The development of TTS confers a particularly unfavourable functional and anatomical ocular prognosis, ultimately requiring enucleation in most cases if untreated. Vitreoretinal (VR) surgery has been successfully applied for treatment and prevention of TTS using both resecting and non-resecting techniques. In this systematic review, we aim to define characteristics of uveal melanomas benefiting the most from secondary VR surgery and to outline the optimal type and timing of VR intervention in such cases. Analysis of the literature reveals that endoresection should be performed within 3 months after radiotherapy to tumours thicker than 7 mm and with a largest basal diameter between 8 mm and 15 mm with post-equatorial location, especially after proton beam treatment. Alternatively, endodrainage remains a valid therapeutic option in eyes with macula-off retinal detachment, tumour diameter larger than 15 mm or ciliary body involvement. VR surgery can be successful in the management of TTS following radiotherapy for uveal melanoma when timing and indication are appropriately evaluated.

We report the clinical findings of a patient with severe bilateral keratectasia 34 years after a penetrating keratoplasty (PK) in both eyes. An otherwise healthy 67-year-old man complained of deterioration of the eyesight in both eyes over the last 6 months. The patient was diagnosed with bilateral keratoconus at the age of 32 years, and he underwent a bilateral PK. At presentation, visual acuity was 20/200 in the right eye and light perception in the left eye. A Pentacam pachymetric map revealed a central pachymetry of 720 µm in the right eye and of 710 µm in the left eye, as well as an average paracentral pachymetry of 436 and 270 µm in the 9-mm zone in the right and the left eye, respectively. Corneal topography revealed bilateral irregular and asymmetric bowing with generalized steepening and high corneal power. We describe a case of bilateral keratectasia 34 years after PK in a patient who was originally diagnosed with bilateral keratoconus.

Two kinds of forces are active in vitreoretinal traction diseases: tangential and anterior-posterior forces. However, tangential forces are less characterized and classified in literature compared to the anterior-posterior ones. Tangential epiretinal forces are mainly due to anomalous posterior vitreous detachment (PVD), vitreoschisis, vitreopapillary adhesion (VPA), and epiretinal membranes (ERMs). Anomalous PVD plays a key role in the formation of the tangential vectorial forces on the retinal surface as consequence of gel liquefaction (synchysis) without sufficient and fast vitreous dehiscence at the vitreoretinal interface. The anomalous and persistent adherence of the posterior hyaloid to the retina can lead to vitreomacular/vitreopapillary adhesion or to a formation of avascular fibrocellular tissue (ERM) resulting from the proliferation and transdifferentiation of hyalocytes resident in the cortical vitreous remnants after vitreoschisis. The right interpretation of the forces involved in the epiretinal tangential tractions helps in a better definition of diagnosis, progression, prognosis, and surgical outcomes of vitreomacular interfaces.

Cystoid macular oedema (CMO) is a major cause of reduced vision following intraocular surgery. Although the aetiology of CMO is not completely clarified, intraocular inflammation is known to play a major role in its development. The macula may develop cytotoxic oedema when the primary lesion and fluid accumulation occur in the parenchymatous cells (intracellular oedema) or vasogenic oedema when the primary defect occurs in the blood-retinal barrier and leads to extracellular fluid accumulation (extracellular oedema). We report on the mechanisms of CMO formation after pars plana vitrectomy and associated surgical procedures and discuss possible therapeutic approaches.

The causes of retinal hypoxia are many and varied. Under hypoxic conditions, a variety of soluble factors are secreted into the vitreous cavity including growth factors, cytokines, and chemokines. Cytokines, which usually serve as signals between neighboring cells, are involved in essentially every important biological process, including cell proliferation, inflammation, immunity, migration, fibrosis, tissue repair, and angiogenesis. Cytokines and chemokines are multifunctional mediators that can direct the recruitment of leukocytes to sites of inflammation, promote the process, enhance immune responses, and promote stem cell survival, development, and homeostasis. The modern particle-based flow cytometric analysis is more direct, stable and sensitive than the colorimetric readout of the conventional ELISA but, similar to ELISA, is influenced by vitreous hemorrhage, disruption of the blood-retina barrier, and high serum levels of a specific protein. Finding patterns in the expression of inflammatory cytokines specific to a particular disease can substantially contribute to the understanding of its basic mechanism and to the development of a targeted therapy.

Eye injury is a significant disabling worldwide health problem. Proliferative Vitreoretinopathy (PVR) is a common complication that develops in up to 40–60% of patients with an open-globe injury. Our knowledge about the pathogenesis of PVR has improved in the last decades. It seems that the introduction of immune cells into the vitreous, like in penetrating ocular trauma, triggers the production of growth factors and cytokines that come in contact with intra-retinal cells, like Müller cells and RPE cells. Growth factors and cytokines drive the cellular responses leading to PVR’s development. Knowledge of the pathobiological and pathophysiological mechanisms involved in posttraumatic PVR is increasing the possibilities of management, and it is hoped that in the future our treatment strategies will evolve, in particular adopting a multidrug approach, and become even more effective in vision recovery. This paper reviews the current literature and clinical trial data on the pathogenesis of PVR and its correlation with ocular trauma and describes the biochemical/molecular events that will be fundamental for the development of novel treatment strategies. This literature review included PubMed articles published from 1979 through 2013. Only studies written in English were included.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications.

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation) and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis) can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch’s membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease.

The human vitreous humour (VH) is a transparent, highly hydrated gel, which occupies the posterior segment of the eye between the lens and the retina. Physiological and pathological conditions of the retina are reflected in the protein composition of the VH, which can be sampled as part of routine surgical procedures. Historically, many studies have investigated levels of individual proteins in VH from healthy and diseased eyes. In the last decade, proteomics analyses have been performed to characterise the proteome of the human VH and explore networks of functionally related proteins, providing insight into the aetiology of diabetic retinopathy and proliferative vitreoretinopathy. Recent proteomic studies on the VH from animal models of autoimmune uveitis have identified new signalling pathways associated to autoimmune triggers and intravitreal inflammation. This paper aims to guide biological scientists through the different proteomic techniques that have been used to analyse the VH and present future perspectives for the study of intravitreal inflammation using proteomic analyses.

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

A correct diagnosis of uveitis is often challenging, given the wide range of possible underlying conditions and the lack of typical phenotypes. Management decisions may be difficult in view of the risk of visual loss with either inappropriate or delayed therapy. Analysis of the vitreous may therefore be used to provide the clinician with valuable information. In this paper, we describe the main clinical situations in which vitreous sampling is indicated and provide some guidance to clinicians for tailoring their requests. These situations include suspected intraocular infection and suspected intraocular malignancy. We describe the principal tests carried out on vitreous samples, including cultures, polymerase chain reaction-based testing, and cytokine analysis. Limitations of the tests used are likely to become less as more advanced testing methods are introduced. The importance of selecting the appropriate investigations to support a clinical suspicion is emphasised, as is the interpretation of test results within a clinical context.

Vitreous body is an intraocular structure, origin of diverse pathologies, but is also the place where cells and inflammatory mediators are released coming from several pathologic processes. These inflammatory reactions can happen in any other ocular location like choroid, retina, optic nerve, or ciliary body and vitreous humor constitutes a stagnant reservoir for these resulting substances and debris. Through the recent techniques of vitreous collecting, handling, and analysis, increasingly more sophisticated and with fewer complications, cellularity and molecules in the vitreous of challenging pathologies for the ophthalmologist can now be studied. The most usefulness for vitreous diagnosis would be the masquerade syndromes, and the best exponent in this group is the primary vitreoretinal lymphoma (PVRL), in which cytology and an IL-10/IL-6 ratio more than 1 is fundamental for the diagnosis.