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.

Comparison between invasive and noninvasive techniques of evaluation of microvascular structural alterations.

BACKGROUND: The evaluation of the morphological characteristics of small resistance arteries in humans is challenging. The gold standard method is generally considered to be the measurement by wire or pressure micromyography of the media-to-lumen ratio of subcutaneous small vessels obtained by local biopsies. However, noninvasive techniques for the evaluation of retinal arterioles were recently proposed; in particular, two approaches, scanning laser Doppler flowmetry (SLDF) and adaptive optics, seem to provide useful information; both of them provide an estimation of the wall-to-lumen ratio (WLR) of retinal arterioles. Moreover, a noninvasive measurement of basal and total capillary density may be obtained by videomicroscopy/capillaroscopy. No direct comparison of these three noninvasive techniques in the same population was previously performed; in particular, adaptive optics was never validated against micromyography. METHODS: In the current study, we enrolled 41 controls and patients: 12 normotensive lean controls, 12 essential hypertensive lean patients, nine normotensive obese patients and eight hypertensive obese patients undergoing elective surgery. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance artery structure was assessed by wire micromyography and the media-to-lumen ratio was calculated. WLR of retinal arterioles was obtained by SLDF and adaptive optics. Functional (basal) and structural (total) microvascular density was evaluated by capillaroscopy before and after venous congestion. RESULTS AND CONCLUSION: Our data suggest that adaptive optics has a substantial advantage over SLDF in terms of evaluation of microvascular morphology, as WLR measured with adaptive optics is more closely correlated with the M/L of subcutaneous small arteries (r = 0.84, P < 0.001 vs. r = 0.52, P < 0.05, slopes of the relations: P < 0.01 adaptive optics vs. SLDF). In addition, the reproducibility of the evaluation of the WLR with adaptive optics is far better, as compared with SLDF, as intraobserver and interobserver variation coefficients are clearly smaller. This may be important in terms of clinical evaluation of microvascular morphology in a clinical setting, as micromyography has substantial limitations in its clinical application due to the local invasiveness of the procedure.

Carotid stiffness is significantly correlated with wall-to-lumen ratio of retinal arterioles.

BACKGROUD AND PURPOSE: Wall-to-lumen ratio of retinal arterioles (W/L ratio) might serve as an in-vivo parameter of microvascular damage. No study has investigated the relationship between carotid stiffness and W/L ratio of retinal arteries. Therefore, the aim of the current study was to assess the correlation between local carotid stiffness, as assessed by echotracking technique, and W/L ratio of retinal arterioles, as assessed by noninvasive flowmetry in normotensive patients and in patients with primary hypertension. METHODS: Two hundred and twenty-seven patients underwent renal arteries W/L ratio and local carotid-pulse wave velocity (carotid PWV) measurement. One hundred and fifteen patients had a diagnosis of primary hypertension, whereas 112 were normotensive patients. RESULTS: W/L ratio and carotid PWV were both related with clinic SBP (r = 0.17, P < 0.05; r = 0.50, P < 0.001), clinic pulse pressure (r = 0.22, P < 0.001; r = 0.55, P < 0.001), carotid SBP (r = 0.18, P < 0.05; r = 0.51, P < 0.001) and carotid pulse pressure (r = 0.24, P < 0.001; r = 0.56, P < 0.001). W/L ratio was correlated with carotid PWV (r = 0.18, P < 0.005). At multivariate analysis, carotid PWV remained independently associated with W/L ratio. CONCLUSION: In hypertensive and normotensive patients, carotid stiffness is significantly correlated with W/L ratio of retinal arteries, independently of possible confounders.

Comparison of lercanidipine plus hydrochlorothiazide vs. lercanidipine plus enalapril on micro and macrocirculation in patients with mild essential hypertension.

Dihydropyridine calcium channel blockers may possess antioxidant properties, and might improve micro and macrovascular structure and function. Combination treatment with an ACE inhibitor may have additional advantages, compared with a thiazide diuretic. The aim of the present study is to investigate the effects of a short-term treatment with lercanidipine, and to compare two combination treatments: lercanidipine + enalapril vs. lercanidipine + hydrochlorothiazide on structural alterations in retinal arterioles, on skin capillary density and on large artery distensibility. Thirty essential hypertension patients are included in the study, and treated for 4 weeks with lercanidipine 20 mg per day orally. Then, they were treated for 6 months with lercanidipine + enalapril (n = 15) or lercanidipine + hydrochlorothiazide (n = 15) combinations. Investigations were performed on basal condition, after appropriate wash out of previous treatments, after 4 weeks of lercanidipine monotherapy treatment, and at the end of the combination treatment. Non-invasive measurements of wall-to-lumen ratio (WLR) and other morphological parameters of retinal arterioles were performed using either scanning laser Doppler flowmetry or adaptive optics. Capillary density was evaluated by capillaroscopy, while pulse wave velocity was measured, and central blood pressures were assessed by pressure waveform analysis. A significant improvement of WLR and other indices of retinal artery structure is observed with both technical approaches after treatment with lercanidipine alone, with a further improvement after treatment with lercanidipine + enalapril, while after treatment with lercanidipine + hydrochlorothiazide, the improvement is partially blunted. Central systolic and diastolic blood pressures are similarly reduced by both therapeutic strategies. Capillary density is increased only after treatment with lercanidipine + enalapril. In conclusion, lercanidipine both in monotherapy and in combination with enalapril but not with hydrochlorothiazide is able to improve microvascular structure; on the other hand, a decrease in central blood pressure is observed with both therapeutic combinations.

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.

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 Structural Alterations in Humans.

BACKGROUND: 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. In addition, it was demonstrated in animal models that TREGs may prevent angiotensin II-induced hypertension and vascular injury/inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular structural alterations. METHODS: For this purpose, 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. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph and the media to lumen ratio (M/L) was calculated. In addition, retinal arteriolar structure was evaluated noninvasively by scanning laser Doppler flowmetry. Capillary density in the nailfold, dorsum of the finger, and forearm were evaluated by videomicroscopy. A peripheral blood sample was obtained before surgery for assessment of T-lymphocyte subpopulations by flow cytometry. RESULTS: Significant negative correlations were observed between indices of microvascular structure (M/L of subcutaneous small arteries and wall to lumen ratio of retinal arterioles) and circulating TREG lymphocytes. A direct correlation was observed between M/L of subcutaneous small arteries and circulating Th17 lymphocytes. In addition, total capillary density was correlated with a TREG effector memory subpopulation. CONCLUSION: Our data suggest that some lymphocyte subpopulations may be related to microvascular remodeling, confirming previous animal data, and opening therapeutic possibilities.

Controversies over the role of internal limiting membrane peeling during vitrectomy in macular hole surgery.

Surgical management of an idiopathic macular hole consists of vitrectomy to release vitreofoveal traction and intraocular tamponade to flatten and reappose the hole's edges. The intentional atraumatic removal of the internal limiting membrane has been proposed as cost-effective option in macular hole surgery. The internal limiting membrane contributes to tangential traction at the edges of the hole and acts as a platform on which glial cells proliferate. Removal of the internal limiting membrane increases the elasticity of the denuded macula and improves the anatomical success rate; however, the visual consequences of this surgical maneuver are still not fully known. We discuss the beneficial and adverse effects associated with internal limiting membrane peeling in macular hole surgery, highlighting the internal limiting membrane's role in macular hole etiology and pathogenesis and the anatomical and functional findings after its removal.

From the analysis of pharmacologic vitreolysis to the comprehension of ocriplasmin safety.

INTRODUCTION: Pharmacologic vitreolysis is a strategy used to treat anomalous posterior vitreous detachment, by weakening vitreoretinal adhesion with an intravitreal drug. Pharmacologic vitreolysis facilitates surgery, and abnormalities of the vitreoretinal interface including vitreomacular traction (VMT) and early stage macular hole (MH) could be resolved. Ocriplasmin is a recombinant protease, active against fibronectin and laminin, which are important components of the vitreoretinal interface. Ocriplasmin has been approved for symptomatic treatment of VMT and MH with visible traction, and it functions by dissolving the proteins that link the vitreous to the macula, thereby creating a complete posterior vitreous detachment (PVD). AREAS COVERED: This paper reviews the current knowledge and status of investigations regarding the use of ocriplasmin for pharmacologic vitreolysis and its safety. EXPERT OPINION: Ocriplasmin is a non-specific enzyme; therefore, it dissolves vitreal proteins as well as possibly proteins associated with visual function in the retina, choroid, and lens. Ocular adverse events (OAEs) of ocriplasmin include transient visual loss, intraocular inflammation, vitreous floaters, lens opacification, zonular instability of the lens, and intraocular hemorrhage. The prevalence of the OAEs is very low; however, on rare occasions, they can result in widespread retinal dysfunction. Research into the acute and long-term safety of ocriplasmin is required.

Pharmacokinetic and Pharmacodynamic Properties of Anti-VEGF Drugs After Intravitreal Injection.

Subretinal neovascularization and pathologic ocular angiogenesis are common causes of progressive, irreversible impairment of central vision, and dramatically affect quality of life. Anti-vascular endothelial growth factor (anti-VEGF) therapy has improved the quality of life for many patients with age-related macular degeneration, diabetic retinopathy, and other ocular diseases involving neovascularization and edema. In these pathologies, the inhibition of intraocular VEGF is the only therapy that can preserve vision. Four anti-VEGF drugs are currently used to treat ocular neovascularization; pegaptanib, ranibizumab, and aflibercept have been approved for this condition, while bevacizumab can be used off-label. Anti-VEGF therapy is administered regularly for many months or years because its suspension or discontinuation may cause recurrence of neovascularization. On the other hand, VEGF is necessary for the survival of retinal and choroidal endothelial cells. Experimental studies in animal models have shown that local inhibition of VEGF causes thinning and atrophy of the choriocapillaris and degeneration of photoreceptors, primarily cones. These studies combined with clinical experience indicated that prolonged VEGF inhibition could impair retinal function. Moreover, anti-VEGF compounds can cross the blood-retina barrier, enter the systemic circulation, and inhibit serum VEGF. Since circulating VEGF protects blood vessel integrity, prolonged anti-VEGF treatment could induce thromboembolic adverse events from vascular causes such as heart attack and stroke, and even death. The ocular dosing regimen and systemic toxicity of anti-VEGF compounds are therefore central concerns. A better understanding of this topic requires knowledge of the metabolism, tissue distribution, and clearance of anti-VEGF compounds. This manuscript reviews the properties of anti-VEGF compounds following intravitreal administration.

Current Trends about Inner Limiting Membrane Peeling in Surgery for Epiretinal Membranes.

The inner limiting membrane (ILM) is the basement membrane of the Müller cells and can act as a scaffold for cellular proliferation in the pathophysiology of disorders affecting the vitreomacular interface. The atraumatic removal of the macular ILM has been proposed for treating various forms of tractional maculopathy in particular for macular pucker. In the last decade, the removal of ILM has become a routine practice in the surgery of the epiretinal membranes (ERMs), with good anatomical results. However many recent studies showed that ILM peeling is a procedure that can cause immediate traumatic effects and progressive modification on the underlying inner retinal layers. Moreover, it is unclear whether ILM peeling is helpful to improve vision after surgery for ERM. In this review, we describe the current understanding about ILM peeling and highlight the beneficial and adverse effects associated with this surgical procedure.

Efficacy and vitreous levels of topical NSAIDs.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed medications and are routinely used for their analgesic, antipyretic, and anti-inflammatory properties. Because of their potent cyclooxygenase-inhibitory activity, they can inhibit pro-inflammatory prostaglandin synthesis, leading to complex inflammatory cascades. NSAIDs have been broadly used systemically for many decades and have recently become commercially available in the form of topical ophthalmic formulations. NSAIDs are weak acids with pKa values mostly between 3.5 and 4.5 and are poorly water-soluble. New, aqueous ophthalmic solutions of NSAIDs that afford better tissue penetration have recently been developed. In ophthalmological practice, topical NSAIDs are mostly used to stabilize pupillary dilation during intraocular surgery, manage postoperative pain and inflammation, and treat pseudophakic cystoid macular edema. AREAS COVERED: This review focuses on the vitreous penetration of topical NSAIDs and their potential clinical applications in the treatment of retinal diseases. EXPERT OPINION: A growing body of evidence suggests that NSAIDs may be beneficial in the treatment of age-related macular degeneration, diabetic retinopathy, and ocular tumors. Recent studies from our group and other authors have shown that the vitreous levels of NSAID exceed the median inhibitory concentration, which can significantly decrease vitreous PGE2 levels.

Heavy silicone oil and intraocular inflammation.

In the past two decades, many advances have been made in vitrectomy instrumentation, surgical techniques, and the use of different tamponade agents. These agents serve close retinal breaks, confine eventual retinal redetachment, and prevent proliferative vitreoretinopathy (PVR). Long-acting gases and silicone oil are effective internal tamponade agents; however, because their specific gravity is lower than that of the vitreous fluid, they may provide adequate support for the superior retina but lack efficacy for the inferior retina, especially when the fill is subtotal. Thus, a specific role may exist for an internal tamponade agent with a higher specific gravity, such as heavy silicone oils (HSOs), Densiron 68, Oxane HD, HWS 45-300, HWS 46-3000, and HeavySil. Some clinical evidence seems to presume that heavy tamponades are more prone to intraocular inflammation than standard silicone if they remain in the eye for several months. In this review, we discuss the fundamental clinical and biochemical/molecular mechanisms involved in the inflammatory response after the use of heavy tamponade: toxicity due to impurities or instability of the agent, direct toxicity and immunogenicity, oil emulsification, and mechanical injury due to gravity. The physical and chemical properties of various HSOs and their efficacy and safety profiles are also described.

Effects of a long-term treatment with aliskiren or ramipril on structural alterations of subcutaneous small-resistance arteries of diabetic hypertensive patients.

Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non-insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non-insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non-insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure-lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non-insulin-dependent diabetes mellitus.

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

INTRODUCTION: Anti-VEGF therapy improved the quality of life for millions of patients suffering from wet age-related macular degeneration (wet-AMD); unfortunately, this therapy involves multiple injections over many years. The administration of anti-VEGF can overcome the blood-retinal barrier with agents entering the systemic circulation and causing a significant decrease in VEGF serum concentration. Although circulating VEGF protects the integrity and patency of vessels, prolonged anti-VEGF treatment has the potential to increase the risk of thromboembolic events. AREAS COVERED: In this review, we discuss the safety data from recent trials involving available anti-VEGF drugs. EXPERT OPINION: During the 2 years of follow-up in the relevant clinical trials, the rates of serious adverse events such as stroke, heart attack and death were similar for patients treated with different anti-VEGF drugs. Moreover the arterial thrombotic risk appears sufficiently low when compared with the natural incidence of arterial thrombotic events in this category of elderly patients and acceptably balanced against the advantage of improved vision. Since the use of these drugs is likely to become increasingly widespread and prolonged, it is desirable that the scientific community improves the pharmacovigilance program on all anti-VEGF drugs, expanding knowledge with studies that compares head to head all four compounds belonging to anti-VEGF armamentarium.

Relationship of wall-to-lumen ratio of retinal arterioles with clinic and 24-hour blood pressure.

Wall-to-lumen ratio of retinal arterioles might serve as an in vivo parameter of vascular damage. We analyzed the impact of brachial clinic blood pressure (BP), of central BP, and of 24-hour BP on wall-to-lumen ratio (WLR) of retinal arterioles. In 295 subjects (147 men; age range, 22-72 years; mean age, 54±7 years), WLR of retinal arterioles was assessed in vivo using scanning laser Doppler flowmetry. In addition, clinic and 24-hour BP values were measured. Central hemodynamics was assessed by pulse wave analysis. In treated patients with essential hypertension (n=100), a higher WLR (0.29±0.18 versus 0.23±0.13; P=0.009) was observed in comparison with normotensive individuals (n=119); no significant differences were observed between treated and untreated hypertensive patients (0.29±0.18 versus 0.28±0.18; P=0.7). WLR of retinal arterioles was significantly related to clinic systolic (r=0.18; P=0.002) and pulse pressure (r=0.20; P=0.001), to 24-hour systolic (r=0.25; P=0.0001) and pulse pressure (r=0.17; P=0.005), and to central systolic (r=0.16; P=0.006) and pulse pressure (r=0.18; P=0.002). Multiple regression analysis revealed that only mean systolic 24-hour BP was independently associated with an increased WLR of retinal arterioles. In this large group of hypertensive patients and normotensive individuals, 24-hour systolic BP seems to be the strongest determinant of increased WLR of retinal arterioles.

Effect of antihypertensive treatment on microvascular structure, central blood pressure and oxidative stress in patients with mild essential hypertension.

BACKGROUND: It has been previously demonstrated that dihydropyridine calcium channel blockers may possess antioxidant properties and might improve vascular structure. Combination treatment with an angiotensin-converting enzyme inhibitor may have additional advantages, compared with a thiazide diuretic, in this regard. The aim of the present study was, therefore, to investigate the effects of a short-term treatment with lercanidipine, and to compare two combination treatments: lercanidipine + enalapril vs. lercanidipine + hydrochlorothiazide on structural alterations in retinal arterioles, on skin capillary density and on large artery distensibility. PATIENTS AND METHODS: Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine 20 mg per day orally. Then they were treated for 6 months with lercanidipine + enalapril (n=10) or lercanidipine + hydrochlorothiazide (n=10) combinations. Investigations were performed in basal condition, after appropriate washout of previous treatments, after 4 weeks of lercanidipine monotherapy treatment, and at the end of the combination treatment. Non-invasive measurements of wall-to-lumen ratio (W/L) and other morphological parameters of retinal arterioles using scanning laser Doppler flowmetry were performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). Capillary density was evaluated by capillaroscopy, whereas pulse wave velocity and central blood pressure were assessed by the Sphygmo-Cor device (AtCor Medical West Ryde, Australia). RESULTS: A significant improvement of W/L and of other indices of retinal artery structure was observed after treatment with lercanidipine alone, with a further improvement after treatment with lercanidipine + enalapril, whereas after treatment with lercanidipine + hydrochlorothiazide the improvement was no longer observed. A similar behaviour was observed for central SBP and DBP. Capillary density was increased only after treatment with lercanidipine + enalapril. CONCLUSION: Lercanidipine both in monotherapy and in combination with enalapril, was able to improve microvascular structure and to decrease central blood pressure, being thus a useful approach for both reducing blood pressure and improving vascular alterations in hypertension.

Quality of vision in patients implanted with aspherical and spherical intraocular lens: Intraindividual comparison.

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.

Proliferative vitreoretinopathy after eye injuries: an overexpression of growth factors and cytokines leading to a retinal keloid.

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.

High doses of cobalt induce optic and auditory neuropathy.

The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined.