Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction.

In the face of the global epidemic of diabetes, it is critical that we update our knowledge about the pathogenesis of diabetes and the related micro alterations on the vascular network in the body. This may ultimately lead to early diagnosis and novel treatment options for delaying the progression of diabetic complications. Research has recently revealed the pivotal role of endothelin in the pathogenesis of diabetic complications, particularly in the regulation of the capillary flow, which is affected in the course of retinopathy. Although there are several reviews on various approaches to the treatment of diabetes, including normalization of glucose and fat metabolism, no reviews in literature have focused on the endothelin system as a therapeutic target or early indicator of diabetic microangiopathy. In this review, we summarize some of the experimental and clinical evidence suggesting that current therapeutic approaches to diabetes may include the modulation of the blood concentration of compounds of the endothelin system. In addition, we will briefly discuss the beneficial effects produced by the inhibition of the production of high levels of endothelin in vasculopathy, with focus on diabetic retinopathy. The cutting-edge technology currently widely used in opththalmology, such as the OCT angiography, allows us to detect very early retinal morphological changes alongside alterations in choroidal and retinal vascular network. Combination of such changes with highly sensitive measurements of alterations in serum concentrations of endothelin may lead to more efficient early detection and treatment of diabetes and related macro/microvascular complications.

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.

Antibodies reacting with Simian Virus 40 capsid protein mimotopes in serum samples from patients affected by uveal melanoma.

The uveal melanoma (UM) is the most common human intraocular tumour. Simian Virus 40 (SV-40) is a small DNA tumor virus detected in some malignancies, including the cutaneous melanoma. In this study an indirect ELISA using synthetic peptides that mimic SV-40 antigens, was employed to detect antibodies against SV-40 in serum samples from UM patients. Our report indicates a significant higher prevalence of antibodies against SV-40 capsid protein antigens in serum samples from UM patients compared to controls. Our data suggest an association between UM and SV-40, indicating that patients affected by uveal melanoma tested SV-40-positive could be treated by innovative therapies.

Inflammaging: should this term be suitable for age related macular degeneration too?

INTRODUCTION: Inflammaging is a phenomenon triggered by the conjunction of chronic repetitive and subclinical inflammation from external aggressors and internal inflammatory mechanisms due to the progressive degradation of systems such as the mitochondrial function. Age-related macular degeneration is the leading cause of blindness and visual impairment in patients older than 60 years in developed countries. DISCUSSION: Remarkable correlations have been documented between common or rare immunological/inflammatory gene polymorphisms and AMD, unequivocally indicating the involvement of inflammation and immune-mediated processes (complement activation) in the pathogenesis of this disease. CONCLUSION: Altogether these factors also drive this pathologic condition under the general heading of "Inflammaging".

Mechanism of inflammation in age-related macular degeneration: an up-to-date on genetic landmarks.

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.

Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report.

BACKGROUND: The etiology of primary cutaneous anaplastic large-cell CD30+ lymphoma is largely unknown, and although an infectious involvement has been suspected, the implication of infectious agents in its pathogenesis is still unclear. FINDINGS: We report the case of a HIV-negative patient referred to our hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical excision was performed and histological analysis evidenced a primary cutaneous anaplastic large-cell lymphoma. Due to the ocular localization and to the prominent angiogenic component of the lesion, molecular analyses for the detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the presence of an infection by both pathogens in surgical biopsy and in peripheral blood mononuclear cells. CONCLUSIONS: These findings suggest for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised and HIV-negative subjects. This potential pathogenic association, if confirmed, could provide potential indications for future therapy.

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.

Relationship between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles evaluated noninvasively by scanning laser Doppler flowmetry.

BACKGROUND: Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media-to-lumen ratio, are frequently present in hypertensive and/or diabetic patients, and may represent the earliest alteration observed. Furthermore, media-to-lumen ratio of small arteries evaluated by micromyography has a strong prognostic significance; however, its extensive evaluation is limited by the invasivity of the assessment, since a biopsy of subcutaneous fat is needed. Noninvasive measurement of wall-to-lumen of retinal arterioles using scanning laser Doppler flowmetry (SLDF) has recently been introduced. However, this new technique has not yet been compared to micromyographic measurement, generally considered the gold standard approach. METHODS AND RESULTS: We investigated 40 individuals and patients, 24 of them were hypertensive patients and 16 normotensive individuals. All patients underwent a biopsy of subcutaneous fat during an elective surgical intervention. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and media-to-lumen ratio was measured. In addition, an evaluation of wall-to-lumen ratio of retinal arterioles by SLDF was performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). A close correlation was observed between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles (r = 0.76, P < 0.001; P < 0.001, r(2) = 0.57). CONCLUSION: A noninvasive and easily repeatable procedure (intraobserver and interobserver variation coefficient <13%) such as an evaluation of the arterioles in the fundus oculi by SLDF may provide similar information regarding microvascular morphology compared with an invasive, accurate and prognostically relevant micromyographic measurement of media-to-lumen ratio of subcutaneous small arteries.

Good epidemiologic practice in retinitis pigmentosa: from phenotyping to biobanking.

Inherited retinal dystrophies, such as retinitis pigmentosa (RP), include a group of relatively rare hereditary diseases caused by mutations in genes that code for proteins involved in the maintenance and function of the photoreceptor cells (cones and rods). The different forms of RP consist of progressive neurodegenerative disorders which are generally related to various and severe limitations of visual performances. In the course of typical RP (rod-cone dystrophy), the affected individuals first experience night-blindness and/or visual field constriction (secondary to rod dysfunctions), followed by variable alterations of the central vision (due to cone damages). On the other hand, during the atypical form of RP (cone-rod dystrophy), the cone's functionalities are prevalently disrupted in comparison with the rod's ones. The basic diagnosis of RP relies upon the documentation of unremitting loss in photoreceptor activity by electroretinogram and/or visual field testing. The prevalence of all RP typologies is variably reported in about one case for each 3000-5000 individuals, with a total of about two millions of affected persons worldwide. The inherited retinal dystrophies are sometimes the epiphenomenon of a complex framework (syndromic RP), but more often they represent an isolated disorder (about 85-90 % of cases). Although 200 causative RP mutations have been hitherto detected in more than 100 different genes, the molecular defect is identifiable in just about the 50% of the analyzed patients with RP. Not only the RP genotypes are very heterogeneous, but also the patients with the same mutation can be affected by different phenotypic manifestations. RP can be inherited as autosomal dominant, autosomal recessive or X-linked trait, and many sporadic forms are diagnosed in patients with no affected relatives. Dissecting the clinico-genetic complexity of RP has become an attainable objective by means of large-scale research projects, in which the collaboration between ophthalmologists, geneticists, and epidemiologists becomes a crucial aspect. In the present review, the main issues regarding clinical phenotyping and epidemiologic criticisms of RP are focused, especially highlighting the importance of both standardization of the diagnostic protocols and appropriateness of the disease's registration systems.

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.

Pharmacogenetic aspects in therapeutic management of subfoveal choroidal neovascularisation: role of factor XIII-A 185 T-allele.

In Western Countries, the occurrence of choroidal neovascularization (CNV) secondary to different forms of macular degeneration represents a common cause of blindness. Particularly, age-related macular degeneration (AMD) and pathologic myopia (PM) are the most frequent diseases related to CNV development. At present, the combined employment of drugs acting against vascular endothelial growth factor (anti-VEGF) and photodynamic therapy with verteporfin (PDT-V) is a promising therapeutic strategy for neovascular macular degenerations. However, this approach inevitably leads to an increase in health-resource utilization. In several clusters of patients treated for CNV, correlations among common gene polymorphisms implicated in coagulation- or complement-cascade and different levels of, respectively, post-PDT-V or post-anti-VEGF benefit have been reported. Factor XIII-A G185T substitution (rs5985), a frequent anti-thrombophilic genetic variant of Caucasian ethnic groups, unequivocally influences a worsening of the CNV responsiveness to PDT-V in patients affected by either AMD- or PM-related CNV. These coherent pharmacogenetic findings point out the opportunities to: i. optimize the eligibility criteria of PDT-V and, ii. customize the interventional strategy against CNV, for finally minimizing the socio-economic burden of neovascular macular degenerations.

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.

Impact of coagulation-balance gene predictors on efficacy of photodynamic therapy for choroidal neovascularization in pathologic myopia.

PURPOSE: To investigate whether different coagulation-balance genetic backgrounds might explain the variable clinical outcomes detected, after a single photodynamic therapy with verteporfin (PDT-V), in Caucasian patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM). DESIGN: Retrospective, consecutive, nonrandomized, interventional cases series. PARTICIPANTS: Two hundred thirty-four patients exclusively treated with standardized PDT-V for the presence of PM-related classic CNV. METHODS: The enrolled patients were subdivided as responders or nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Three common gene polymorphisms, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, and methionine synthase reductase A66G, were genotyped by polymerase chain reaction in each patient. MAIN OUTCOME MEASURES: The measures of CNV responsiveness to PDT-V were the changes, respect to baseline, of fluorescein angiography CNV leakage, greatest linear dimension, and area of the lesion. Logistic regression analyses were performed to explore the predictive role of phenotypic (patient's age, baseline visual acuity, and baseline CNV area) and genotypic (all the mentioned mutations) variables regarding PDT-V efficacy. RESULTS: Responders to PDT-V were overrepresented within carriers of methylenetetrahydrofolate reductase 677 T-allele (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.8-5.4; P = 0.001) and, to a minor extent, among patients with better visual acuity at baseline (OR, 11.8; 95% CI, 1.6-88.0; P = 0.02). However, predictors of PDT-V lack of efficacy were patient's age (OR, 0.73; 95% CI, 0.62-0.86; P = 0.01) and, especially, factor XIII-A 185 GT/TT genotypes (OR, 0.19; 95% CI, 0.11-0.35; P = 0.0001). All the other considered predictive factors did not significantly influence the CNV responsiveness to PDT-V. CONCLUSIONS: These findings document the presence of pharmacogenetic correlations between common coagulation-balance gene polymorphisms and different CNV responsiveness to PDT-V in Caucasian patients with neovascular PM.

Predictive role of gene polymorphisms affecting thrombin-generation pathway in variable efficacy of photodynamic therapy for neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) represents the leading cause of central blindness in developed countries. The majority of severe vision loss occurs in the neovascular form of AMD, generally characterized by the presence of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) and drugs acting against vascular endothelial growth factor are the most commonly employed treatments for AMD-related subfoveal CNV. The combined use of both these strategies is the most promising therapeutic approach towards this harmful disease. The therapeutic action of PDT-V depends to a photochemical perturbation of thrombo-coagulative processes within CNV. Predictive correlations between peculiar coagulation-balance gene polymorphisms and different levels of post-PDT-V benefit have been recently documented in Caucasian patients with neovascular AMD. Particularly, heterozygous A-allele carriers of factor V Leiden 1691 or prothrombin 20210 gene are characterized by a greater possibility to exhibit clinical benefit after PDT-V. Both mutations induce thrombophilia increasing the thrombin generation in plasma and, thus, they can consistently intensify the photothrombotic phase of the therapeutic CNV occlusion. In prospect, considering the different individual susceptibility to PDT-V, a preoperative assessment of the genotypic thrombophilic background could optimize the eligibility criteria of this intriguing treatment. This review summarizes some of the recent published patents on treatment of neovascular AMD, with a particular attention to PDT-V application in combined therapeutic modalities.

Predictive role of C677T MTHFR polymorphism in variable efficacy of photodynamic therapy for neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) complicated by subfoveal choroidal neovascularization (CNV) is the leading cause of severe central blindness in developed countries. AMD-related CNVs are distinguishable in classic and occult subtypes, characterized by variable natural history and different responsiveness to therapeutic procedures. Combined and repeated use of photodynamic therapy with verteporfin (PDT-V) and antiangiogenic drugs represents the most promising strategy against neovascular AMD, but it is unavoidably associated with mounting health-resource utilization. Predictive correlations between peculiar coagulation-balance gene variants and different levels of post-PDT-V benefit have recently been documented in Caucasians with AMD-related CNVs. In particular, methylenetetrahydrofolate reductase C677T substitution, a common thrombophilic folate pathway genotypic polymorphism, influences a better CNV responsiveness to PDT-V in classic- but not in occult-CNV cases. These pharmacogenetic findings indicate the opportunities to optimize the eligibility criteria of PDT-V and/or to perform this intriguing therapy in a customized manner, for finally minimizing the socio-economic burden of neovascular AMD.

Conjunctival sac fluid contains elevated levels of soluble TRAIL: implications for the anti-tumoral surveillance of the anterior surface of the eye.

Little is known on the ability of different epithelia to release soluble TNF-related apoptosis-inducing ligand (TRAIL) and the relevance of TRAIL secretion by epithelial cells is still incompletely understood. On these bases, we have measured the concentration of soluble TRAIL by ELISA in the conjunctival sac fluid. It was the highest ever detected in a biological fluid (mean value of 26,800 pg/ml), being approximately 20-fold greater than that found in human saliva and >200-fold greater than that detected in human serum. On the other hand, osteoprotegerin, the soluble decoy receptor of TRAIL, was almost undetectable in the conjunctival sac fluid. Of note, the levels of soluble TRAIL measured in conjunctival sac fluid were in the range able to induce in vitro apoptosis of lymphoma cells. By in situ immunohistochemistry, TRAIL protein expression was predominantly detected in the corneal epithelium and, to a less extent, in the conjunctival epithelium. By flow cytometry analysis, membrane-associated TRAIL was documented in isolated corneal epithelial cells obtained from patients undergoing photorefractive keratectomy (PRK). The key contribution provided by corneal epithelium to the production of soluble TRAIL was underscored in time-course experiments, in which a marked decrease of the levels of soluble TRAIL in the conjunctival sac fluid was demonstrated 1 day after PRK followed by a progressive recovery at days 5-30 after PRK. Taken together, our findings strongly support a major role of soluble TRAIL in protecting cornea and conjunctiva from tumor formation and/or invasion.

Coagulation gene predictors of photodynamic therapy for occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: The clinical records of consecutive patients with AMD-related occult CNV, treated with PDT-V for evidence of disease progression, were retrospectively examined. Eighty-four eligible subjects were subdivided into responders and nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Six gene polymorphisms (i.e., factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G) were genotyped in each patient. Logistic regression analyses were performed to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS: Regression models documented that PDT-V nonresponders were more frequently patients with the hyperfibrinolytic G185T mutation of factor XIII-A (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.73; P < 0.01). Univariate logistic regression was indicative of an overrepresentation of PDT-V responders among the combined carriers of thrombophilic factor V 1691A and prothrombin 20210A alleles (OR = 3.8; 95% CI: 0.94-15.6; P = 0.07). All the other predictors considered did not significantly influence the short-term CNV responsiveness to PDT-V. CONCLUSIONS: These data provide evidence of the presence of a pharmacogenetic relationship between peculiar coagulation-balance genetic backgrounds and different levels of PDT-V effectiveness in patients with AMD with occult CNV.

Circadian changes of intraocular pressure and ocular perfusion pressure after timolol or latanoprost in Caucasians with normal-tension glaucoma.

PURPOSE: To evaluate the circadian effects on intraocular pressure (IOP) and ocular perfusion pressure (OPP) of 0.5% timolol or 0.005% latanoprost in Caucasian patients affected by normal-tension glaucoma (NTG). PATIENTS AND METHODS: In this crossover trial, 30 consecutive NTG subjects underwent three 24-hour assessments of IOP, blood pressure (BP), heart rate (HR), and OPP [calculated according to the formula OPP = (1/3 systolic BP + 2/3 diastolic BP) x 2/3 - IOP]: at baseline, and after 1-month treatment with timolol or latanoprost. These parameters were recorded at 4 a.m., 8 a.m., noon, 4 p.m., 8 p.m., and midnight. RESULTS: Both timolol and latanoprost reduced IOP (p < 0.001), with a difference in favour of latanoprost of 1.3 mmHg (95% CI 0.9, 1.6; p < 0.001). After timolol, BP and HR decreased with respect to baseline (p < 0.001). Latanoprost increased mean OPP (3.6 mmHg, 95% CI 2.9, 4.3; p < 0.001), whereas timolol did not improve it. CONCLUSIONS: Latanoprost induces an IOP reduction greater than timolol, also achieving a better circadian flattening of the IOP curve. Only latanoprost significantly increased mean 24-hour OPP. The management of Caucasian NTG patients should be critically realized, considering the 24-hour influence of each IOP-lowering drug on the ocular blood perfusion.

Selective serotonin reuptake inhibitors: a review of its effects on intraocular pressure.

The increase in serotonin (5-HT) neurotransmission is considered to be one of the most efficacious medical approach to depression and its related disorders. The selective serotonin reuptake inhibitors (SSRIs) represent the most widely antidepressive drugs utilized in the medical treatment of depressed patients. Currently available SSRIs include fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram and escitalopram. The primary SSRIs pharmacological action's mechanism consists in the presynaptic inhibition on the serotonin reuptake, with an increased availability of this amine into the synaptic cleft. Serotonin produces its effects as a consequence of interactions with appropriate receptors. Seven distinct families of 5-HT receptors have been identified (5-HT(1) to 5-HT(7)), and subpopulations have been described for several of these. The interaction between serotonin and post-synaptic receptors mediates a wide range of functions. The SSRIs have a very favorable safety profile, although clinical signs of several unexpected pathologic events are often misdiagnosed, in particular, those regarding the eye. In all cases reported in the literature the angle-closure glaucoma represents the most important SSRIs-related ocular adverse event. Thus, it is not quite hazardous to hypothesize that also the other reported and unspecified visual disturbances could be attributed - at least in some cases - to IOP modifications. The knowledge of SSRIs individual tolerability, angle-closure predisposition and critical IOP could be important goals able to avoid further and more dangerous ocular side effects.