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PubMedDate not supplied

Retinal angiomatous proliferation treated with a combination of intravitreal triamcinolone acetonide and photodynamic therapy with verteporfin.

PURPOSE: Retinal angiomatous proliferation (RAP) is a particularly aggressive form of exudative age-related macular degeneration. Response to laser photocoagulation or to photodynamic therapy (PDT) alone is often disappointing. The purpose of this study was to determine whether intravitreal triamcinolone acetate (TA) injections followed by PDT in eyes with early stage RAP may be effective. METHODS: Prospective uncontrolled study, enrolling 11 patients (11 eyes) with stage 2 RAP, treated with intravitreal TA injection followed by PDT. Patients with large pigment epithelium detachment, RAP stage 3, or pre-existing glaucoma and known steroid responders were excluded. All patients underwent a complete ophthalmic examination including fluorescein and indocyanine green (ICG) angiography and optical coherence tomography (OCT-3) at baseline and at 1, 3, 6, and 12 months. Informed consent was obtained from all patients. RESULTS: Mean follow-up was 14.9 months (range 6 C21 months). Mean age was 82 years. In four patients a small pigment epithelium detachment was found on tomography. Initial visual acuity (VA) ranged from 0.1 to 0.6 on the Snellen scale. After calculating the logarithmic values the authors found an initial mean VA of logMAR 0.61, which improved by 1.5, 0.9, and 0.9 log lines after 3, 6, and 12 months, respectively. Although the VA gain from baseline tended to decrease with time, only 2 patients (18%) had an actual loss of acuity>or=3 lines). Retreatment was required in 5 eyes. CONCLUSIONS: In this prospective pilot study examining the use of intravitreal TA followed by PDT with verteporfin in eyes with stage 2 RAP, without a large pigment epithelium detachment, the authors found a potential benefit in terms of stabilization or even improvement of vision.

Aged↗
PubMedDate not supplied

Protocols for screening and treatment of diabetic retinopathy in Europe.

Diabetes eye complications, and particularly diabetic retinopathy, are the major cause of blindness in the working age groups of industrialised countries. Laser photocoagulation has been proven to reduce blindness due to retinopathy by at least 60% but even more patients would benefit if treatment were delivered at an early enough stage. High risk retinopathy, though, does not cause visual symptoms and when the latter occur it is often too late to reverse them. Hence, a screening programme for diabetic retinopathy should aim at detecting patients at risk when they can still be effectively treated. This can be obtained by regularly checking the patients' eyes. Its target, as defined by the joint World Health Organisation/International Diabetes Federation Saint Vincent Declaration Working Group, is to reduce diabetes-related blindness by one third or more in the next 5 years. The number of persons to be screened is high, 30,000/million total population/year, but available data indicate that this is feasible and that the initial investments in professional and material resources are more than justified by the reduction of preventable blindness and of the financial burdens that go with it. Indeed, prevention of the major cause of blindness in the working age should rate the same priority as other widely deployed programmes, such as those to screen for cancer, neonatal hypothyroidism and phenylketonuria. The concerted action of government health departments, patients' and professional associations will be vital for the successful implementation of this programme. The texts of this document (a protocol for the screening of diabetic retinopathy and cataract), Appendix 1 (data collection card) and Appendix 2 (informative leaflet for the patients) were approved by 57 specialists, representing 30 diabetic and ophthalmic societies from 21 European countries, and endorsed for translation into all European languages and distribution at the appropriate levels.

Cataract Extraction↗
PubMed2005

NO role in EPC function.

The nitric oxide pathway plays an important role in modulating endothelial progenitor cell function, playing a critical role in blood vessel repair in response to injury.

Animals↗
PubMed2004

Ocular angiogenesis: translating preclinical indications to successful clinical development.

Angiogenesis-related ocular diseases such as age-related macular degeneration (AMD) or diabetic retinopathy have a high socioeconomic impact in western countries and are the leading causes of blindness. Conventional treatment modalities for AMD are of limited success. Inhibition of new vessel formation and targeting of pathological vessels seem to be the best choice in AMD. A variety of animal models mimic the relevant aspects of choroidal neovascularisation (CNV) and allow for therapy screening. Preclinical and clinical studies show that a variety of different strategies are very promising. Stategies include inhibition or blocking of vascular endothelial growth factor, a key player in angiogenesis), blocking specific receptors, application of naturally occurring angiogenesis inhibitors and gene therapy. However, the multistep pathways involved in ocular angiogenesis suggest that a cocktail approach is required for effective long-term treatment and prevention of CNV.

Animals↗
PubMed2007

2nd Ophthalmic Drug Development and Delivery Summit.

The Second Annual Ophthalmic Drug Development and Delivery Summit was held on 19 - 20 September 2006 in San Diego, CA, US. The 2-day symposium, having a highly focused theme, was packed with cutting-edge science, insightful overviews and networking opportunities. With a total of 11 recognized specialists presenting reviews and recent results in the advancement of ocular drug development and delivery, the invited expert speaking faculty presented the latest preclinical and clinical developments in novel ophthalmic therapies and drug delivery technology. The talks included various case studies from primary investigators and pharmaceutical companies touching upon key topics: updates on current clinical trials, study design issues, sustained delivery to the eye, views of the vitreous space as a drug reservoir, new developments in dry and wet age-related macular degeneration and diabetic retinopathy, formulation for optimal drug delivery, differences and similarities in developing drugs for the eye compared with other targets, pharmacokinetics, novel ocular delivery methods and devices, delivery of proteins and peptides, focal drug delivery, non-invasive drug delivery to the eye, neuroprotection challenges, in vitro and in vivo models for glaucoma and angiogenesis for early efficacy estimation, and toxicology. Overall, the 2-day annual symposium continues to grow as an efficient platform for fostering discussion on a range of scientific topics and challenges and avenues for building collaborative partnerships in ophthalmic drug development.

Animals↗
PubMed2005

[Pathological features of diabetic retinopathy].

Diabetic retinopathy continues to be an important cause of adult blindness among Americans and Brazilians. There are determinant environmental factors in the development of diabetic retinopathy although increasing evidence suggests a genetic component in diabetic retinopathy. The advances made during the last two decades with the purpose of improving the understanding of the mechanisms involved in the development and progression of diabetic retinopathy have prompted this review. This article has the purpose of revising and updating concepts about the ocular physiopathology of diabetes mellitus.

Adult↗
PubMed1999

Chemotherapy for retinoblastoma: a current topic.

Retinoblastoma is the most common primary intraocular tumour in children, with an incidence of 1 in 15,000 live births. Treatment strategies for retinoblastoma have gradually evolved over the past few decades. There has been a trend away from enucleation (removal of the eye) and external beam radiation therapy toward focal 'conservative' treatments. Every effort has been made to save the child's life with preservation of eye and sight, if possible. Primary enucleation continues to be the commonly used method of treatment for retinoblastoma. It is employed in situations where eyes contain large tumours, long standing retinal detachments, neovascular glaucoma and suspicion of optic nerve invasion or extrascleral extension. Most of these eyes either have or are expected to have no useful vision. Radiation therapy continues to be an effective treatment option for retinoblastoma. However, external beam radiotherapy has unfortunately been associated with secondary non-ocular cancers in the field of radiation (primarily in children carrying the RB-1 germline mutation). Ophthalmic plaque brachytherapy has a more focal and shielded radiation field, and may carry less risk. Unfortunately, its applicability is limited to small to medium-sized retinoblastomas in accessible locations. Cryotherapy and transpupillary thermotherapy (TTT) have been used to provide control of selected small tumours. TTT is an advanced laser system adapted to the indirect ophthalmoscope which provides flexible nonsurgical treatment for small retinoblastomas. Recent research in the treatment of retinoblastoma has concentrated on methods of combining chemotherapy with other local treatment modalities (TTT, radiotherapy, cryotherapy). This approach combines the principle of chemotherapeutic debulking in paediatric oncology with conservative focal therapies in ophthalmology. Termed chemoreduction, intravenous or subconjunctival chemotherapy is used to debulk the initial tumour volume and allow for local treatment with TTT, cryotherapy and plaque radiotherapy. Cyclosporin has been added to the chemotherapy regimen in several centres. Other clinical settings where chemotherapy is considered are situations where the histopathology suggests a high risk for metastatic disease and where there is extraocular extension. There is no consensus that chemotherapy is needed when choroidal invasion is observed on histopathology. However, in patients where the retinoblastoma is noted beyond the cut end of the optic nerve or if there is disruption of the sclera with microscopic invasion of the orbital tissue, treatment has been helpful. Systemic and intrathecal chemotherapy with local and cranial radiotherapy has improved the survival of these patients. Most recently, the use of new chemotherapy modalities with haematopoietic stem cell rescue or local radiotherapy has increased the survival of patients with distant metastasis. Nevertheless, the prognosis of patients with central nervous system involvement is still poor.

Animals↗
PubMed2005

DNA and RNA aptamers as modulators of protein function.

The SELEX technique (systematic evolution of ligands by exponential enrichment) is a combinatorial library approach in which DNA or RNA molecules are selected by their ability to bind their protein targets with high affinity and specificity. The isolated molecules are referred to as aptamers (from aptus = Latin "to fit"). First, RNA and DNA aptamers were identified that bind to proteins naturally interacting with nucleic acids, or to small organic molecules such as ATP. In the following years, the use of the SELEX technique was extended to isolate oligonucleotide ligands for a wide range of proteins of importance for therapy, and diagnostics. Since these RNA and DNA molecules bind their targets with similar affinities as antibodies, and are able to distinguish between isotypes of an enzyme, aptamers have been also called synthetic antibodies. Recently, the use of in vitro selection methods to isolate protein inhibitors has been extended to complex targets, such as receptors that are only functional in their membrane-bound form, cells, and trypanosomes. RNA aptamers have been expressed in living cells where they inhibit a protein implicated in intracellular signal transduction. The utility of aptamers for in vivo experiments, and diagnostic and therapeutic purposes, is considerably enhanced by introducing chemical modifications into the oligonucleotides to provide resistance against enzymatic degradation in body fluids. Recently, such inhibitors have been evolved for a great variety of targets, including receptors, growth factors, and adhesion molecules implicated in disease. Furthermore, some results were already obtained in animal models and clinical trials.

Animals↗
PubMed1994

The combined effects of diabetes and ionising radiation on the rat retina: an ultrastructural study.

The combined effect of STZ-diabetes and ionising radiation on the rat retina was investigated. Wistar rats, which had been diabetic for 6 months, were irradiated with a single dose of x-rays (1500 cGy) and the ultrastructural effects evaluated at 4-10 mths post-irradiation. At 4 months post-irradiation, the outer nuclear layer of the retina was greatly reduced in thickness and the photoreceptor outer segments were disorganised and reduced in length. In addition, the nerve fibre layer contained many cytoid bodies and there were many redundant basement membrane tubes throughout the inner retina. By 6 months post-irradiation, the photoreceptor cells were virtually absent, bringing the external limiting membrane into close apposition to the RPE. Throughout large areas of the outer retina, RPE cells were hypertrophic and some had proliferated into the inner retina. In many regions, proliferating retinal capillaries were observed within the RPE layer, and at 8 months post-irradiation, some vessels extended into the inner retina accompanied by RPE cells. At 10 months post-irradiation, the RPE was atrophic and degenerative with retinal glial cells coming into contact with Bruch's membrane. In some areas, the glia which had breached Bruch's membrane had invaded the underlying choroid. Where glial cells contacted the choriocapillaries, the vessels assumed the appearance of retinal vessels with plump endothelia and no fenestrations. This study has described a progressive inner retinal ischemia, with cytoid bodies, capillary non-perfusion and general atrophy of the inner retina intensifying markedly with increasing post-irradiation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The effects of bFGF on RCS rat eyes.

Basic fibroblast growth factor (bFGF) has been implicated as a factor in retinal differentiation and disease. Recent studies have shown that subretinal or intravitreal injections of bFGF delay the retinal degeneration of the RCS rat but the global nature of this effect has been quantified for few test animals and the mechanism underlying this effect is not understood. In order to determine more accurately the global effects of intravitreal bFGF and to further elucidate the mechanism of bFGF promoted photoreceptor cell saving, we injected one of three bFGF doses into the vitreal cavities of young RCS rats. Using measurements from several eyes, we confirmed that a single intravitreal bFGF injection globally delays the RCS dystrophy. Test eyes contained fewer debris zone macrophages and more inner retinal macrophages than did control eyes at 1 month post injection. As bFGF's saving effect waned, the number of inner retinal macrophages decreased and the number of debris zone macrophages increased toward control levels. Dose-dependent cataract formation occurred in 100% of test eyes. Eyes that received the highest bFGF dose showed increased retinal vascularization at 1, 2 and 3 months post injection. The possible relationships between bFGF promoted photoreceptor survival and our findings are discussed.

Animals↗
PubMed1999

Decreasing retinal photocoagulation damage: principles and techniques.

Conventional suprathreshold retinal photocoagulation is a destructive procedure, but chorioretinal damage can be decreased by changing laser parameters and clinical endpoints. Laser effects can be localized by decreasing laser wavelength, spot size, and exposure duration, as well as by adopting threshold or subthreshold treatment protocols. Problems with short-pulse treatment regimens can be circumvented by the use of repetitively pulsed laser photocoagulators. Preliminary clinical results with reduced-damage photocoagulation methods are promising and await confirmation in larger, controlled clinical trials.

Choroid↗
PubMed1997

Uveitis in Behçet's disease.

The ocular complications of Behçet's disease are considered one of the major criteria upon which the diagnosis is based. Its complications are frequently sight threatening and require constant attention. The ocular disease is characterized by repeated, explosive ocular inflammatory attacks which get better by themselves, so that in-between attacks there is little or no evidence of inflammatory disease in the eye. The anterior segment can be involved alone, most frequently presenting as a severe anterior uveitis, frequently with hypopyon. This is not associated with a poor visual outcome, and usually treated with topical medication to make the patient more comfortable. However, the anterior segment disease is usually accompanied by recurrent retinal vaso-occlusive disease which is sight threatening if repeated attacks occur. Treatment is with systemic medications, including corticosteroids, cyclosporine, FK506, anti-metabolites, and cytotoxic agents. Complications of the inflammation can include retinal and optic atrophy, vitreous hemorrhage, neovascular glaucoma, and retinal detachment.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Management of retinopathy of prematurity with cryotherapy.

PURPOSE: Newborns at risk for retinopathy of prematurity (ROP) should be examined 4 to 8 weeks postpartum. Various treatment modalities including cryotherapy, are proposed to ablate the retinal proliferation, when serious and progressive ROP is detected. This study stresses as main risk factors low birth weight and short gestational age as pre-disposing to ROP and the efficiency of cryotherapy as a treatment modality. METHODS: One hundred and twenty five newborns were examined before hospital discharge and after oxygen administration was terminated. Patients with suspected ROP returned for frequent follow-up visits. In patients with stage III ROP (ridge with extraretinal fibrovascular proliferation) ablation by cryotherapy was performed. RESULTS: Retinal ridge and extraretinal proliferation characteristic of stage III ROP were detected in ten newborns. All surviving stage III patients were treated with cryoablation and two of them progressed to stage IV. Regression of ROP was observed in eight of the ten treated cases. CONCLUSIONS: With properly planned screening of newborns at risk for ROP, early diagnosis and treatment are possible. Cryotherapy seems to be effective for ablation of the proliferation.

Cryotherapy↗
PubMed1999

N(epsilon)(carboxymethyl)lysin and the AGE receptor RAGE colocalize in age-related macular degeneration.

PURPOSE: To investigate whether glycoxidation products and the receptor for advanced glycation end products (RAGE) are present and colocalize in subfoveal membranes of patients with age-related macular degeneration (ARMD). METHODS: Surgically removed subfoveal fibrovascular membranes from 12 patients, 11 related to ARMD and 1 to an idiopathic membrane, were analyzed for the presence of the glycoxidation product N(epsilon)-(carboxymethyl)lysin (CML), one of the receptors for advanced glycation end products, RAGE, and the activation of NFkB, using immunohistochemistry. RESULTS: CML-like immunoreactivity was found in all ARMD specimens examined adjacent or colocalized with RAGE, but not in the idiopathic membrane. RAGE immunoreactive material was found in CD68-positive cells and in the fibrous matrix. CD68-positive cells and surrounding areas stained for p50, the activated form of NFkB. CONCLUSIONS: These results indicate that glycoxidation products are present in subretinal membranes of patients with ARMD. The concomitant expression of RAGE in these membranes and the finding of activated NFkB is suggestive of an implication of glycoxidation product formation in the pathogenesis of the disease.

Adolescent↗
PubMed2000

Retinal VEGF mRNA measured by SYBR green I fluorescence: A versatile approach to quantitative PCR.

PURPOSE: To determine whether continuous monitoring of SYBR Green I fluorescence provides a reliable and flexible method of quantitative RT-PCR. Our aims were (i) to test whether SYBR Green I analysis could quantify a wide range of known VEGF template concentrations, (ii) to apply this method in an experimental model, and (iii) to determine whether 20 existing primer pairs could be used to quantify their cognate mRNAs. METHODS: Real-time quantitative PCR was performed using a LightCycler rapid thermal cycler (Roche). Retinal VEGF mRNA levels were measured in a murine model of oxygen-induced retinopathy during vaso-obliterative and hypoxic phases. RESULTS: This technique was able to detect as few as 10 control template copies, with quantitative data available routinely for 1000 or more copies. The levels of retinal VEGF mRNA expression followed the hypoxia-induced pattern determined previously by conventional methods. All gene-specific primer pairs which amplify a specific product by conventional PCR were successfully converted to SYBR Green analysis, including those for housekeeping genes glyceraldehyde phosphate dehydrogenase (GAPDH), cyclophilin, and acidic ribosomal phosphoprotein PO (ARP/36B4) and for 28S rRNA. In each case melting curve analysis and agarose gel electrophoresis confirmed the specificity of the amplification product. CONCLUSIONS: The sequence-independent detection of DNA with SYBR Green I means that it can be used to quantify the amplification of any cDNA using gene-specific primers. This rapid and flexible method is ideally suited for researchers in vision science wishing to quantify mRNAs from many different genes because it does not require investment in gene-specific hybridization probes.

Animals↗