Mario R. Romano

Corneal cross-linking as a treatment for keratoconus: Four-year morphologic and clinical outcomes with respect to patient age

PURPOSE To report the 4-year outcomes of corneal cross-linking (CXL) for progressive keratoconus in a population of different age groups. DESIGN Retrospective, single-center, nonrandomized clinical study. PARTICIPANTS Four hundred consecutive eyes treated with corneal CXL for progressive keratoconus from April 2006 through April 2010. INTERVENTION After removal of the epithelium, the cornea was irrigated for 30 minutes with a solution of 0.1% riboflavin and 20% dextran, followed by irradiation with an ultraviolet A light of 3 mW/cm(2) for 30 minutes. MAIN OUTCOME MEASURES Best-corrected visual acuity (BCVA), sphere and cylinder refraction, corneal topography, Scheimpflug tomography, and aberrometry were assessed at baseline and at 1, 6, 12, 24, 36, and 48 months after corneal CXL treatment. The compiled data were stratified according to age (group A, younger than 18 years; group B, 18-29 years; group C, 30-39 years; and group D, older than 40 years). RESULTS Comparative analysis included 400 eyes of 301 patients. Functional results showed a significant increase in BCVA in group A by a mean reduction of -0.11 logarithm of the minimum angle of resolution (logMAR) after 12 months, in group B by a mean reduction of -0.31 logMAR after 36 months, in group C by a mean reduction of -0.33 logMAR after 36 months, and in group D by a mean reduction of -0.26 logMAR after 36 months. Morphologic results showed an analogous regularization of corneal shape with a significant reduction of opposite sector index by a mean value of -0.53 at 12 months in group A, -1.14 at 36 months in group B, -1.10 at 36 months in group C, and -0.55 at 12 months for group D. Optical quality improvement was demonstrated by a mean significant reduction of coma -1.52 μm after 12 months in group A, -1.58 μm after 24 months in group B, -2.57 μm after 36 months for group C, and -0.25 μm after 36 months in group D. CONCLUSIONS Outcomes stratified by age indicate the efficacy of corneal CXL in stabilizing the progression of ectatic disease in all age groups and improving the functional and morphologic parameters in select groups. Results indicated better functional and morphologic results in the population between 18 and 39 years of age. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

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.

Therapeutic Challenges to Retinitis Pigmentosa: From Neuroprotection to Gene Therapy

Syndromic retinitis pigmentosa (RP) is the result of several mutations expressed in rod photoreceptors, over 40 of which have so far been identified. Enormous efforts are being made to relate the advances in unraveling the patho-physiological mechanisms to therapeutic approaches in animal models, and eventually in clinical trials on humans. This review summarizes briefly the current clinical management of RP and focuses on the new exciting treatment possibilities. To date, there is no approved therapy able to stop the evolution of RP or restore vision. The current management includes an attempt at slowing down the degenerative process by vitamin supplementation, trying to treat ocular complications and to provide psychological support to blind patients. Novel therapeutic may be tailored dependant on the stage of the disease and can be divided in three groups. In the early stages, when there are surviving photoreceptors, the first approach would be to try to halt the degeneration by correction of the underlying biochemical abnormality in the visual cycle using gene therapy or pharmacological treatment. A second approach aims to cope with photoreceptor cell death using neurotrophic growth factors or anti-apoptotic factors, reducing the production of retino-toxic molecules, and limiting oxidative damage. In advanced stages, when there are few or no functional photoreceptors, strategies that may benefit include retinal transplantation, electronic retinal implants or a newly described optogenetic technique using a light-activated channel to genetically resensitize remnant cone-photoreceptor cells.

Proteomic Analyses of the Vitreous Humour

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

Can a preoperative bevacizumab injection prevent recurrent postvitrectomy diabetic vitreous haemorrhage

AimsTo evaluate the recurrence rate of vitreous haemorrhage (VH) in patients treated with one intravitreal bevacizumab (IVB) injection (2.5 mg/0.1 ml) before planned pars plana vitrectomy for treatment of diabetic non-clearing VH.MethodsProspective pilot study of 32 eyes of 31 consecutive diabetic patients who underwent IVB injection within 1 week before surgery for persistent VH in the presence of active proliferative diabetic retinopathy. Three masked retinal specialists graded the amount of VH from grade 0 to grade 3 with slit-lamp biomicroscopy. Main outcome measures were the rate of recurrence of the VH, improvement in visual acuity, incidence of cataract formation, and postoperative complications through a follow-up of 6 months.ResultsThe percentage of severe recurrent VH with no fundus details (grade 3) was 3% at 1 week follow-up and 3, 6, and 6% respectively at 1-, 3-, and 6-month follow-up. The mean best-corrected visual acuity (BCVA) improved from 1.6 (1/60) to 0.40 (6/15) logMAR (P=0.02) in 29 out of 32 eyes (91%). In all, 12 out of 22 (54%) phakic eyes developed cataract during the follow-up period, and 10 (31%) of them underwent cataract surgery.ConclusionsOur study suggests that IVB injection few days before planned surgery seems to be efficacious and safe as an adjuvant treatment to prevent rebleeding in eyes undergoing pars plana vitrectomy for treatment of diabetic vitreous haemorrhage. IVB facilitates the surgery and reduces the need for extensive delamination and segmentation, decreasing the possibility of significant early active postoperative VH.

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 PVRs 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.

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 Bruchs 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.

TNF-Alpha Levels in Tears: A Novel Biomarker to Assess the Degree of Diabetic Retinopathy

We assess the level of tumour necrosis factor alpha (TNF-alpha) in tear fluids and other serum parameters associated with diabetes in different degrees of diabetic retinopathy. We have performed a prospective, nonrandomized, observational study. Study population consisted of 16 healthy subjects (controls) and 32 type 2 diabetic patients: 16 affected by proliferative diabetic retinopathy (PDR) and 16 with nonproliferative retinopathy (NDPR, background/preproliferative). Body mass index, urinary albumin, blood glucose, HbA1c, and tear levels of TNF-alpha were measured in all subjects. The value of glycaemia, microalbuminurea, and Body mass index in diabetic retinopathy groups were higher than those in control group (P < 0.05). Glycemia in NPDR: 6.6 mmol/L (range: 5.8–6.3); in PDR: 6.7 mmol/L (range: 6.1–7.2); in control: 5.7 mmol/L (range: 4.9–6.1); microalbuminurea in NPDR: 10.6 mg/L (range: 5.6–20); in PDR: 25.2 mg/L (range: 17–40); in control: 5.3 mg/L (range: 2.6–10); Body mass index in NPDR: 26 Kg/m2 (range: 20.3–40); in PDR: 28 Kg/m2 (range 20.3–52); in control: 21 Kg/m2 (range 19–26). The TNF-alpha concentrations in tears increase with the severity of pathology and were lower in control group than in diabetic subjects. In the end, the level of TNF-alpha is highly correlated with severity of diabetic retinopathy and with nephropathy. Tear fluid collection may be a useful noninvasive method for the detection of proliferative diabetic retinopathy.

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.

Pharmacotherapy of intraocular pressure: part I. Parasympathomimetic, sympathomimetic and sympatholytics.

Elevated intraocular pressure (IOP) has been recognized as the major risk factor for the development of glaucoma and a wide range of options are now available to reduce it: medical treatment, laser, filtering, or cyclodestructive surgery (alone or in combination). All these modalities act by decreasing eye pressure and, thereby, protecting the optic nerve head from a mechanic direct and/or vascular indirect insult. Topical medical therapy represents the first-choice treatment and, in most cases, it effectively controls IOP, avoiding the occurrence of further optic nerve damage. All medications lower IOP in two main ways: decreasing the production of aqueous humour or by increasing its outflow from the eye. Consequently, antiglaucoma drugs either suppress aqueous humour formation (β-adrenergic antagonists, carbonic anhydrase inhibitors, and alpha-2-adrenergic agonists) or raise aqueous humour outflow throughout the conventional (e.g., pilocarpine) or uveoscleral (prostaglandin FP receptor agonists, and prostamides) route. In addition, fixed and unfixed combinations of antiglaucoma compounds have also been available for patients requiring more than one type of medication. This review, which is part one of two (please see Expert Opinion on Pharmacotherapy 10 (17)) briefly considers the characteristics of sympathomimetic, sympatholytics and parasympathomimetic commonly employed in the medical treatment of glaucoma, mainly the primary open-angle form, focusing the discussion on the clinical evidence supporting the use of these three classes of compound.