Denuded Descemet's membrane supports human embryonic stem cell-derived retinal pigment epithelial cell culture.

Recent clinical studies suggest that retinal pigment epithelial (RPE) cell replacement therapy may preserve vision in retinal degenerative diseases. Scaffold-based methods are being tested in ongoing clinical trials for delivering pluripotent-derived RPE cells to the back of the eye. The aim of this study was to investigate human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells survival and behaviour on a decellularized Descemet's Membrane (DM), which may be of clinical relevance in retinal transplantation. DMs were isolated from human donor corneas and treated with thermolysin. The DM surface topology and the efficiency of the denudation method were evaluated by atomic force microscope, scanning electron microscopy and histology. hESC-RPE cells were seeded onto the endothelial-side surface of decellularized DM in order to determine the potential of the membrane to support hESC-RPE cell culture, alongside maintaining their viability. Integrity of the hESC-RPE monolayer was assessed by measuring transepithelial resistance. RPE-specific gene expression and growth factors secretion were assessed to confirm maturation and functionality of the cells over the new substrate. Thermolysin treatment did not affect the integrity of the tissue, thus ensuring a reliable method to standardize the preparation of decellularized DM. 24 hours post-seeding, hESC-RPE cell attachment and initial proliferation rate over the denuded DM were higher than hESC-RPE cells cultured on tissue culture inserts. On the new matrix, hESC-RPE cells succeeded in forming an intact monolayer with mature tight junctions. The resulting cell culture showed characteristic RPE cell morphology and proper protein localization. Gene expression analysis and VEGF secretion demonstrate DM provides supportive scaffolding and inductive properties to enhance hESC-RPE cells maturation. Decellularized DM was shown to be capable of sustaining hESC-RPE cells culture, thus confirming to be potentially a suitable candidate for retinal cell therapy.

Leber Mitochondrial Optic Neuropathy in Pediatric Females With Focus on Very Early Onset Cases.

The aim of this study was to describe the phenotype of Leber hereditary optic neuropathy occurring in pediatric females. This disease generally affects young adult males, but it can occur also in females, and research data in this population is lacking. The very early onset can challenge the diagnosis and delay treatment. We searched PubMed through February 2021 and identified 226 pediatric females with genetically confirmed Leber hereditary optic neuropathy and added a new case of a 3-year-old female. The male-female ratio was 1.8:1; the mean onset age in females was 11 years with the onset at 3 years of age occurring in 3 females only. Acute onset with mild visual impairment was the most common presentation, associated with optic disc edema in 16%. Differential diagnoses are pseudotumor cerebri, optic nerve drusen and optic neuritis. The outcome is poor with partial recovery in 50%, despite some receiving Idebenone therapy.

Diabetic macular edema: Safe and effective treatment with intravitreal triamcinolone acetonide (Taioftal).

PURPOSE: To suggest the safety and efficacy of preservative-free triamcinolone acetonide intravitreal injectable suspension (Taioftal) for the treatment of diabetic macular edema. METHODS: A prospective clinical study involved 49 patients (49 eyes), that were treated with Taioftal and followed-up for six months. Complete ophthalmic examination, including spectral domain optical coherence tomography, was performed at baseline, and at month 1, 3, 6 after the intravitreal injection. Accurate collection and analysis of best-corrected visual acuity (BCVA), central foveal thickness (CFT), intraocular pressure (IOP), and adverse events (AEs) were carried out in order to evaluate visual function and macular morphology before and after treatment. RESULTS: Median BCVA value chosen as comparing statistics was significantly improved at every follow-up time points (gain of 6 letters at month 1, 12 at month 3 -improvement up to 24% at month 3 with stabilization until month 6) compared to baseline, as certified by Kruskal-Wallis rank sum test (P<0.05). Median CFT significantly waned at each follow-up times (decrease of about 65 µm at month 1, 155 at month 3 -reduction up to 28% at month 3 keeping good outcome until month 6) compared to baseline (P<0.05). IOP elevation, with no severe increases, was the most common among spotted AEs (median of 23 mmHg at month 1, 20 at month 3). CONCLUSION: Intravitreal injection of preservative-free triamcinolone (Taioftal) is an effective, safe and inexpensive drug used to improve visual acuity and reduce central foveal thickness in eyes affected by diabetic macular edema during an average time of 6 months. Temporary, never severe, elevation of IOP is totally manageable with topical medications. No serious vision-threatening complications are related to the use of intravitreal triamcinolone injections.

Application of Artificial Intelligence in Targeting Retinal Diseases.

Retinal diseases affect an increasing number of patients worldwide because of the aging population. Request for diagnostic imaging in ophthalmology is ramping up, while the number of specialists keeps shrinking. Cutting-edge technology embedding artificial intelligence (AI) algorithms are thus advocated to help ophthalmologists perform their clinical tasks as well as to provide a source for the advancement of novel biomarkers. In particular, optical coherence tomography (OCT) evaluation of the retina can be augmented by algorithms based on machine learning and deep learning to early detect, qualitatively localize and quantitatively measure epi/intra/subretinal abnormalities or pathological features of macular or neural diseases. In this paper, we discuss the use of AI to facilitate efficacy and accuracy of retinal imaging in those diseases increasingly treated by intravitreal vascular endothelial growth factor (VEGF) inhibitors (i.e. anti-VEGF drugs), also including integration and interpretation features in the process. We review recent advances by AI in diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity that envision a potentially key role of highly automated systems in screening, early diagnosis, grading and individualized therapy. We discuss benefits and critical aspects of automating the evaluation of disease activity, recurrences, the timing of retreatment and therapeutically potential novel targets in ophthalmology. The impact of massive employment of AI to optimize clinical assistance and encourage tailored therapies for distinct patterns of retinal diseases is also discussed.

Curcumin-Based Treatment for Macular Edema from Uncommon Etiologies: Efficacy and Safety Assessment.

The aim of this study was to investigate the efficacy and safety of curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC*; Diabec®-AlfaIntes, Italy) for the treatment of macular edema (ME) from uncommon etiologies. We conducted retrospective interventional case series, reviewing the medical records of patients referred to the Eye Center, Humanitas Hospital, Bergamo due to persistent ME related to uncommon causes and treated by oral administration of CHC. The main outcomes assessed were best-corrected visual acuity (BCVA), central macular thickness (CMT), and the presence of intraretinal and/or subretinal fluid (SRF). Only patients with a minimum follow-up (f/u) of 6 months were included. The occurrence of any adverse effect was registered. Thirty-one eyes of 30 patients were included, with a mean f/u of 8.32 ± 1.77 months. Of them, 9 patients (10 eyes) were affected by postoperative ME and 21 by chronic central serous chorioretinopathy. Median BCVA significantly improved after treatment, changing from 0.3 [0.16-0.5] to 0.1 [0-0.3] logarithm of the minimum angle of resolution (P < .001). Also CMT was significantly improved, as it decreased from 400 [364-438] µm before treatment to 280 [242-307] µm at the last f/u visit (P < .001). The complete absorption of intraretinal/SRF was detected in 23 of 31 eyes (74%) at the final f/u. No adverse effects were registered. In conclusion, treatment with CHC was effective and safe for eyes affected by ME of various uncommon etiologies, resulting in significant improvement of both functional and anatomical outcomes, with the complete resolution of the edema in the majority of cases (74%).

Dexamethasone Implant Produces Better Outcomes than Oral Acetazolamide in Patients with Cystoid Macular Edema Secondary to Retinitis Pigmentosa.

Purpose: To compare the clinical outcome of intravitreal dexamethasone implant versus oral acetazolamide in patients with cystoid macular edema (CME) secondary to retinitis pigmentosa (RP). Design: Multicenter, prospective, propensity-score-matched, comparative study. Methods: Eyes with RP and CME were treated either with intravitreal dexamethasone implant or with oral acetazolamide (500 mg/day). Patients were evaluated monthly and followed up for 12 months. Primary outcome measures were changes in central retinal thickness and best corrected visual acuity (BCVA). Adverse events were recorded. Results: Propensity score matching resulted in 2 groups of 30 eyes each. All patients completed 12 months of follow-up. Mean central retinal thickness decreased from 535 µm at baseline to 208 µm at month 12 in the dexamethasone implant group and from 519 to 339 µm in the oral acetazolamide group (P < 0.001, Student's t-test). Mean BCVA average change from baseline during the study (area-under-the-curve approach) was -0.084 logarithm of the minimum angle of resolution (logMAR) (+4.2 letters) in the dexamethasone implant group and -0.032 (+1.6 letters) in the oral acetazolamide group (P < 0.05, Mann-Whitney U test). Patients in the dexamethasone implant group required on average 1.7 treatments during 1 year of therapy. Conclusions: In this study, intravitreal dexamethasone implant produced better anatomic and functional improvements over oral acetazolamide in patients affected by CME secondary to RP. Larger, randomized clinical trials with longer follow-up are warranted to confirm these data.

Peripheral Intrastromal Hydration Facilitates Safe, Deep Trephination in Corneas of Irregular Thickness.

PURPOSE: To evaluate the feasibility of regularizing the peripheral corneal thickness before deep trephination in highly irregular corneas undergoing deep anterior lamellar keratoplasty (DALK) by means of intrastromal hydration with saline. METHODS: This is an interventional case series including all eyes with irregular peripheral corneal thickness undergoing DALK for any indication between January 1, 2016, and January 1, 2017, at a single tertiary center in Forli, Italy. Before trephination, 1 mL of normal saline was injected intrastromally into each clock hour of peripheral thinning (determined using preoperative pachymetry) using a 30-gauge needle. A deep trephination of 400 to 450 µm was then performed, and DALK was completed as per our previously described technique. Primary outcome measures were perforation during trephination and intraoperative complications, with secondary outcomes of best corrected visual acuity and refraction. RESULTS: Peripheral intrastromal hydration was performed in 61 eyes of 61 patients. Intrastromal hydration ensured a safe trephination without perforation into the anterior chamber (AC) in 59 of 61 eyes. In the 2 cases in which perforation occurred, the perforation site was sutured with a full-thickness suture and the surgery was completed successfully. No cases required conversion to penetrating keratoplasty. Intrastromal injection of 1 mL of normal saline resulted in an increase in corneal thickness of 31%. After surgery, double AC was observed in 3 cases (4.9%), with all cases being managed successfully by air injection into the AC. CONCLUSIONS: Zonal peripheral intrastromal hydration is a feasible technique to enable safe, deep trephination even in corneas of highly irregular thickness.

Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration: an update.

Introduction: Intravitreal anti-VEGF is the most effective therapy for wet AMD, although systemic effects on the endothelium cannot be excluded. Areas covered: The purpose of this review was to evaluate risk of thromboembolic events associated with intravitreal anti-VEGF. Expert opinion: Current data are insufficient to confirm the safety of these compounds, due to the paucity of specific studies. Thus, pharmacovigilance for all anti-VEGF should be improved to verify the true role of anti-VEGF in the occurrence of systemic adverse events.

Comparative assessment of intraocular inflammation following standard or heavy silicone oil tamponade: a prospective study.

PURPOSE: To evaluate the inflammation associated with the use of standard silicone oil (polydimethylsiloxane; PDMS) and heavy silicone oil (HSO) Densiron-68™ in patients undergoing vitrectomy for retinal detachment. MATERIALS AND METHODS: A prospective study was performed involving 35 patients scheduled to undergo vitrectomy for retinal detachment. Patients received PDMS or Densiron-68™ HSO according to superior or inferior retinal localization of the tears, respectively. For assessing the inflammation, prostaglandin E2 (PGE2 ) and interleukin-1α (IL-1α) levels were evaluated in the aqueous. RESULTS: Thirty-five eyes of 35 patients completed the study: 20 eyes received HSO, and 15 eyes received PDMS. The mean aqueous PGE2 level was significantly higher in HSO patients than in PDMS patients (869.16 ± 242.83 pg/ml versus 369.38 ± 209.7 pg/ml, respectively; p < 0.0001). The mean aqueous IL-1α level was also significantly higher in HSO patients than in PDMS patients (81.40 ± 36.9 pg/ml versus 40.8 ± 32.5 pg/ml, respectively; p = 0.002). In HSO, a moderate positive correlation between the endotamponade duration and both PGE2 (r = 0.44; p = 0.05) and IL-1α (r = 0.48; p = 0.033) levels was observed. In PDMS, a strong positive correlation between the endotamponade duration and both PGE2 (r = 0.89; p < 0.0001) and IL-1α (r = 0.68; p = 0.006) levels was observed. CONCLUSION: Although both HSO and PDMS yielded favourable success rates in the surgical treatment of complicated retinal detachments, HSO triggered a more severe inflammatory reaction, in a time-dependent manner.

Torsional phacoemulsification: A pilot study to revise the "harm scale" evaluating the endothelial damage and the visual acuity after cataract surgery.

PURPOSE: To study the effect of torsional phacoemulsification energy on corneal endothelium evaluating the relationship between changes of endothelial cells and postoperative visual acuity. METHODS: This prospective clinical observational cohort study included 50 patients with cataract who underwent torsional phacoemulsification. Sequential quantitative and qualitative morphometric endothelial cell analyses of the cornea were performed four weeks preoperatively and six weeks postoperatively using noncontact specular microscopy. RESULTS: This work confirmed the strong relationship, described by a linear model (one-way ANOVA, R2 = 77.9%, P < 0.0001), between the percentage of endothelial cell loss (ECL%) and the 5-score harm scale. According to the Tukey post-hoc pairwise comparison test, distinct values of ECL% are grouped in 3 subsets. The value of ECL = 10% has been identified as cut-off to discriminate patients with excellent postoperative best-corrected visual acuity (BCVA > 85 letters) from those with just a good/satisfied visual outcome (BCVA ≤ 85 letters). Within the 5-score harm scale, there was a significant correlation among phaco energy intraoperatively delivered and the average endothelial cell loss. CONCLUSIONS: This study confirms the validity of the 5-score harm scale first proposed by Sorrentino and colleagues in 2016. This time, the method categorizes cataracts taking into account nucleus hardness and phaco cumulative dissipated energy. Predicting the harm on corneal endothelium, we can discriminate patients with excellent BCVA and with just good/satisfied BCVA. With torsional phacoemulsification with respect to longitudinal, the percentage of patients who can reach excellent BCVA is remarkably increased.

Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics.

Factor XIII (FXIII) is a key molecule in the field of blood coagulation and in the last decades it has weakened attention within the field of angiogenesis and tissue repair. FXIII positively influences wound healing in several tissues by exerting multiple plasma and cellular functions. In the field of haemostasis, FXIII cross-links the neo formed fibrin fibers and supports platelet adhesion to the damaged sub-endothelium warranting a solid architecture. In addition, the pro-angiogenic functions of FXIII are directed by the interaction of vascular endothelial growth factor receptor 2 (VEGFR2) and the integrin αVß3, on the cell membrane, favouring an important step in the formation of granulation tissue at the wound site for optimal tissue healing. Conversely, the same mechanisms could lead to undesired increased neovascularisation, for example in inflammatory bowel disease or in the retinal degenerative pathologies. The classical symptoms of FXIII deficiency span from intracranial haemorrhage to delay bleeding or the staying of chronic wounds in the skin including impaired mucosal healing. In this view, FXIII bridges primary haemostasis, coagulation and definite tissue healing. Another important recently discovered function ascribed to FXIII is its ability to limit bacterial spreading from the lesion by incorporating specific macromolecules addressed to cellular infiltration, favouring in turn cell migration and survival, as observed also in fibrin-heart cultures for stem cell recruitment. In the field of the novel prognostic biomarkers, the monitoring of the residual circulating FXIII level during acute myocardial infarction has been considered predictive of the post-myocardial infarction healing. Accordingly, adequate FXIII levels can drive and predict the prognosis of complex diseases and the outcome of the associated therapies or interventions. In addition, peculiar pharmacogenetics aspects of the FXIII gene are of extraordinary interest. The present review accounts for the recognized role of FXIII in the healing process and gives some examples on how to use it as prognostic biological/ molecular marker or as potential tailored therapeutic molecule in complex diseases.

Topical nonsteroidal anti-inflammatory drugs for macular edema.

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.

Intravitreal pegaptanib sodium (Macugen) for treatment of myopic choroidal neovascularization: a morphologic and functional study.

BACKGROUND: To report the morphologic and functional outcomes resulting from the use of intravitreal pegaptanib (IVP) sodium (Macugen) in patients with myopic choroidal neovascularization. METHODS: An open-label, nonrandomized, prospective clinical trial was performed. Morphologic outcome, such as foveal thickness, was assessed by optical coherence tomography, whereas functional outcomes were assessed by best-corrected visual acuity and microperimetry. Treatment protocol consisted of 3 consecutive IVP (0.3 mg/0.05 mL; baseline, 6th week, and 12th week). Follow-up checks were scheduled at the following intervals: baseline, 18, 24, 36, and 48 weeks. RESULTS: Twenty eyes from 20 patients were studied. All patients completed follow-up at 48 weeks. After IVP, a significant decrease in foveal thickness occurred (-20%), and at the end of follow-up, choroidal neovascularization closure was obtained in all eyes. An improvement of functional parameters was recorded in all patients (best-corrected visual acuity from 25.5 ± 8.09 letters to 45.5 ± 8.16 letters, P < 0.0001; microperimetry from 8.40 ± 2.14 dB to 10.8 ± 2.05 dB, P < 0.01). The mean number of IVP was 3, and none of patients met the re-treatment criterion during the entire follow-up period. Neither ocular nor systemic side effects were observed. CONCLUSION: The findings demonstrate that the selective inhibition of VEGF-165 isoform by IVP is an effective treatment for myopic choroidal neovascularization.

Mechanism of inflammation in age-related macular degeneration.

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.

Interaction between perfluorcarbon liquid and heavy silicone oil: risk factor for "sticky oil" formation.

PURPOSE: To investigate in vitro the interaction between perfluorcarbon liquids (PFCLs) and heavy silicone oils (HSOs). METHODS: Interactions between different kinds of PFCL [perfluoro-n-octane (PFO) or perfluorodecaline (PFD)] and HSO (either alkane or ether) were studied in vitro by incubating fluids for 7 days at regulated temperatures. The samples were divided into two groups: Group A, PFCL (PFO or PFD) + 5 ml of HSO (silicone oil + alkane or ether) and Group B, HSO (silicone oil + alkane or ether) without PFCL. Each sample was kept at 36°C for 7 days. HSOs were then removed with a 20 g, 7 mm-long cannula under 600 mm Hg of vacuum pressure at two different temperatures: 36 and 22°C. The time needed to remove the oils and the presence of opacity was recorded. Each experiment was repeated three times. RESULTS: In vitro, interactions between PFCL and HSO oil led to the formation of hyper-viscous solutions with significative increase in aspiration time in Group A. (P = 0.006, Kruskal-Wallis test) Temperature was also found to affect HSOs' saturation, as a decrease in temperature determined an increase in opacity and shear viscosity of the solution (P = 0.02, Kruskal-Wallis test). No differences between alkane and ether (P = 0.74) and n-octane and decaline (P = 0.56) was found. CONCLUSION: Interactions between PFCL-HSO and variation in temperature lead to the formation of hyper-viscous solutions that could be described as "sticky oil".

Intravitreal pegaptanib sodium (Macugen®) for treatment of diabetic macular oedema: a morphologic and functional study.

AIMS: To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes. METHODS: A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections. RESULTS: Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported. CONCLUSIONS: Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO.

Genetic predictors of response to photodynamictherapy.

In Western countries, therapeutic management of patients affected by choroidal neovascularization (CNV) secondary to different typologies of macular degeneration represents a major health care problem. Age-related macular degeneration is the disease most frequently associated with CNV development. Schematically, CNVs can be distinguished into classic and occult subtypes, which are characterized by variable natural history and different responsiveness to some therapeutic procedures. At present, the dramatic vision loss due to CNV can be mainly treated by two interventional strategies, which are utilizable in either single or combined modalities: photodynamic therapy with verteporfin (PDT-V), and intravitreal administration of drugs acting against vascular endothelial growth factor. The combined use of PDT-V and anti-angiogenic drugs represents one of the most promising strategies against neovascular macular degeneration, but it unavoidably results in an expensive increase in health resource utilization. However, the positive data from several studies serve as a basis for reconsidering the role of PDT-V, which has undergone a renaissance prompted by the need for a more rational therapeutic approach toward CNV. New pharmacogenetic knowledge of PDT-V points to exploratory prospects to optimize the clinical application of this intriguing photothrombotic procedure. In fact, a Medline search provides data regarding the role of several single nucleotide polymorphisms (SNPs) as genetic predictors of CNV responsiveness to PDT-V. Specifically, correlations between SNPs and different levels of PDT-V efficacy have been detected by examining the gene variants influencing (i) thrombo-coagulative pathways, i.e. methylenetetrahydrofolate reductase (MTHFR) 677C>T (rs1801133), factor V (F5) 1691G>A (rs6025), prothrombin (F2) 20210G>A (rs1799963), and factor XIII-A (F13A1) 185G>T (rs5985); (ii) complement activation and/or inflammatory processes, i.e. complement factor H (CFH) 1277T>C (rs1061170), high-temperature requirement factor A1 (HTRA1) promoter -512G>A (rs11200638), and two variants of the C-reactive protein (CRP) gene (rs2808635 and rs876538); and (iii) production and bioavailability of vascular endothelial growth factor (VEGFA -2578C>A [rs699947] and rs2146323). This article critically evaluates both the clinical plausibility and the opportunity to utilize the most important SNP-response interactions of PDT-V for an effective upgrade of the current anti-CNV therapeutic scenario. In addition, the pharmacogenetics of a very severe post-PDT-V adverse event, i.e. a decrease in acute vision, is briefly discussed. A comprehensive appraisal of the findings reviewed in this article should be carefully considered to design future trials aimed at verifying (after proper genotypic stratification of the enrolled patients) whether these innovative pharmacogenetic approaches will be able to improve the multifaceted interventional management of neovascular macular degeneration.

Systemic adverse drug reactions secondary to anti-VEGF intravitreal injection in patients with neovascular age-related macular degeneration.

The wet form of age related macular degeneration (AMD), known also as exudative or neovascular, is characterized by the formation of a pathological choroidal neovascular membrane (CNV) responsible for most cases of severe blindness. Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein acting as a growth factor selective for endothelial cells; it regulates angiogenesis and enhances vascular permeability and plays a leading role in this disorder. The consistent association between CNV and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular AMD. The importance of VEGF for the development of AMD-related CNV has led to the development of a strategy able to block its pathologic effects. The rationale is that a blockade of VEGF actions could be effective in arresting choroidal angiogenesis and also reducing the vascular permeability, which is frequently the main cause of visual acuity deterioration. However, VEGF has also important functions in vascular physiology. The effects of anti-VEGF therapy may inhibit these functions. Herein we report the systemic adverse events secondary to intravitreal administration of these compounds i.e. the main cardiovascular effects (thrombosis, hemorrhage, hypertension, proteinuria), as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thrombophlebitis.

Intraocular pressure changes following the use of silicone oil or Densiron 68 as endotamponade in pars plana vitrectomy.

OBJECTIVE: To compare the effects of standard silicone oil 5700 (SSO) and heavy silicone oil (HSO) such as Densiron(®) 68 on intraocular pressure (IOP). MATERIALS AND METHODS: Retrospective case series including 180 eyes (105 treated with SSO and 75 with HSO). IOP was measured before surgery, 1 day after, and then at 1-, 3-, 6-, and 12-month follow-ups. RESULTS: In the SSO group, a significant increase in IOP occurred in 14% of the eyes (15/105) at 1 day postoperatively, and persisted in 11.4% (12/105) at 1-month follow-up. In the HSO group, a persistent elevated IOP was recorded in 20% of the eyes (15/75) at 1 day postoperatively, and in 16% (12/75) at 1-month follow-up. At 12-month follow-up, mean IOP was 16.7 ± 8.7 mmHg and 19.7 ± 3.8 mmHg, respectively, in the SSO and HSO groups. The difference between the 2 groups was always not significant. CONCLUSION: Overall, the use of Densiron 68 was not associated with higher IOP values as compared with SSO.

Inflammatory mediators and angiogenic factors in choroidal neovascularization: pathogenetic interactions and therapeutic implications.

Choroidal neovascularization (CNV) is a common and severe complication in heterogeneous diseases affecting the posterior segment of the eye, the most frequent being represented by age-related macular degeneration. Although the term may suggest just a vascular pathological condition, CNV is more properly definable as an aberrant tissue invasion of endothelial and inflammatory cells, in which both angiogenesis and inflammation are involved. Experimental and clinical evidences show that vascular endothelial growth factor is a key signal in promoting angiogenesis. However, many other molecules, distinctive of the inflammatory response, act as neovascular activators in CNV. These include fibroblast growth factor, transforming growth factor, tumor necrosis factor, interleukins, and complement. This paper reviews the role of inflammatory mediators and angiogenic factors in the development of CNV, proposing pathogenetic assumptions of mutual interaction. As an extension of this concept, new therapeutic approaches geared to have an effect on both the vascular and the extravascular components of CNV are discussed.