Stavros A. Dimitrakos

Evolving European guidance on the medical management of neovascular age related macular degeneration

Background: Until recently, only two options were available for the treatment of choroidal neovascularisation (CNV) associated with age related macular degeneration (AMD)—thermal laser photocoagulation and photodynamic therapy with verteporfin (PDT-V). However, new treatments for CNV are in development, and data from phase III clinical trials of some of these pharmacological interventions are now available. In light of these new data, expert guidance is required to enable retina specialists with expertise in the management of AMD to select and use the most appropriate therapies for the treatment of neovascular AMD. Methods: Consensus from a round table of European retina specialists was obtained based on best available scientific data. Data rated at evidence levels 1 and 2 were evaluated for laser photocoagulation, PDT-V, pegaptanib sodium, and ranibizumab. Other treatments discussed are anecortave acetate, triamcinolone acetonide, bevacizumab, rostaporfin (SnET2), squalamine, and transpupillary thermotherapy. Results: PDT-V is currently recommended for subfoveal lesions with predominantly classic CNV, or with occult with no classic CNV with evidence of recent disease progression and a lesion size ⩽4 Macular Photocoagulation Study (MPS) disc areas (DA). The new classes of anti-angiogenic agents—namely, pegaptanib sodium and ranibizumab (the latter when peer reviewed phase III data become available) are recommended for subfoveal lesions with any proportion of classic CNV or occult with no classic CNV. For juxtafoveal classic CNV, PDT-V or anti-angiogenic therapy should be considered if the new vessels are so close to the fovea that laser photocoagulation would almost certainly extend under the centre of the foveal avascular zone. For all other well demarcated juxtafoveal lesions and for extrafoveal classic lesions, laser photocoagulation remains the standard treatment. Therapy should be undertaken within 1 week of the fluorescein angiogram on which the clinical decision to treat is based. At each follow up, fluorescein angiography should be performed and best corrected visual acuity measured as a minimum requirement. Conclusions: These recommendations provide evidence based guidance for the choice and use of non-surgical therapies for the management of neovascular AMD. Revisions of the recommendations may be required as new data become available.

Macular hole surgery without prone positioning

PurposeTo investigate the role of vitrectomy without prone posturing in the anatomic and functional outcome of macular hole surgery (MHS).MethodsForty-one consecutive eyes of 41 patients with stage II–IV full-thickness macular holes underwent pars plana vitrectomy and 16% C3F8 tamponade. In 25 cases posturing group (P), subjects were instructed to assume prone positioning for 10 days postoperatively, whereas in 16 cases non-posturing group (NP) patients were advised to avoid lying supine but no other posturing instructions were given. Preoperative, intraoperative and postoperative clinical data were collected, with macular hole closure rate and change in LogMAR visual acuity, contrast sensitivity, metamorphopsia, and 25-Visual Function Questionnaire (VFQ-25) being the primary outcome measures.ResultsOver a mean follow-up of 4.2±1.2 months, anatomical hole closure was noted in 22/25 (88%) and 14/16 (87.5%) in groups P and NP respectively. Visual acuity improved by a mean of eight letters and there was no significant difference in the two groups (P=0.724). Similarly, postoperative prone posturing did not have an effect on the final contrast sensitivity, metamorphopsia, and VFQ-25 composite scores (P=0.238, P=0.472, and P=0.87, respectively). However, eyes in group NP developed significantly more severe cataract in the early postoperative period (P=0.02).ConclusionsProne posturing following MHS provides no functional or anatomic benefit but it is associated with slower progression of cataract. Combined phacovitrectomy without face down positioning may be considered for all phakic patients undergoing MHS.

Angiogenic Growth Factors and their Inhibitors in Diabetic Retinopathy

Diabetic retinopathy is considered one of the vision-threatening diseases among working-age population. The pathogenesis of the disease is regarded multifactorial and complex: capillary basement membrane thickening, loss of pericytes, microaneuryms, loss of endothelial cells, blood retinal barrier breakdown and other anatomic lesions might contribute to macular edema and/or neovascularization the two major and sight threatening complications of diabetic retinopathy. A number of proangiogenic, angiogenic and antiangiogenic factors are involved in the pathogenesis and progression of diabetic retinal disease, Vascular Endothelial Growth Factor (VEGF) being one of the most important. Other growth factors, which are known to participate in the pathogenesis of the disease, are: Platelet Derived Growth Factor (PDGF), Fibroblast Growth Factor (FGF), Hepatocyte Growth Factor (HGF), Transforming Growth Factor (TGF), Placental Endothelial Cell Growth Factor (PlGF), Connective Tissue Growth Factor (CTGF). Other molecules that are involved in the disease mechanisms are: intergrins, angiopoietins, protein kinase C (PKC), ephrins, interleukins, leptin, angiotensin, monocyte chemotactic protein (MCP), vascular cell adhesion molecule (VCAM), tissue plasminogen activator (TPA), and extracellular matrix metalloproteinases (ECM-MMPs). However, the intraocular concentration of angiogenic factors is counterbalanced by the ocular synthesis of several antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin, thrombospondin, steroids, atrial natriuretic peptide (ANP), inteferon, aptamer, monoclonal antibodies, VEGF receptor blocker, VEGF gene suppressors, intracellular signal transduction inhibitors, and extracellular matrix antagonists. Growth stimulation or inhibition by these factors depends on the state of development and differentiation of the target tissue. The mechanisms of angiogenesis factor action are very different and most factors are multipotential; they stimulate proliferation or differentiation of endothelial cells. This review attempts to briefly outline the knowledge about peptide growth factor involvement in diabetic retinopathy. Further ongoing research may provide better understanding of molecular mechanisms, disease pathogenesis and therapeutic interactions.

Vitreous and serum levels of vascular endothelial growth factor and platelet-derived growth factor and their correlation in patients with non-proliferative diabetic retinopathy and clinically significant macula oedema.

Purpose:  To investigate possible correlations between vitreous and/or serum levels of platelet‐derived growth factor isoforms (PDGF‐AA, ‐AB and ‐BB) with parameters associated with non‐proliferative diabetic retinopathy (NPDR) and clinically significant macula oedema (CSMO); to compare the results to relevant results regarding vascular endothelial growth factor (VEGF), which is an established growth factor affecting NPDR.

Vitreous and Serum Levels of Platelet-Derived Growth Factor and Their Correlation in Patients with Proliferative Diabetic Retinopathy

Purpose: We investigated possible correlations between vitreous and/or serum levels of platelet derived growth factor isoforms (PDGF-AA, -AB, -BB) with parameters associated with proliferative diabetic retinopathy (PDR), and compared the results to vascular endothelial growth factor (VEGF), which is an established growth factor affecting PDR. Methods: Thirty-one patients with PDR and 15 non-diabetic patients were included in the study. Vitreous and serum samples were obtained during vitrectomy. PDGF-AA, -AB, and -BB, as well as VEGF, were measured by enzyme-linked immunosorbent assay. Results: PDGF-AA, -AB, -BB, and VEGF were all expressed in serum and vitreous of controls and patients with PDR. The levels of all PDGF isoforms and VEGF in vitreous were significantly increased in the PDR group, as compared to controls. No such differences were evident in serum. PDGF-AA and PDGF-BB correlated significantly to the severity but not the activity of PDR. PDGF-AB and -BB were significantly lower in vitreous of patients with pre-performed complete panretinal photocoagulation (PRP) as compared to incomplete or without PRP. PDGF did not correlate significantly to fibrovascular tissue, on the disc or elsewhere, to long-standing vitreous hemorrhage, to tractional retinal detachment, or to posterior vitreous detachment. PDGF or VEGF in vitreous or serum of PDR patients did not correlate with the serum levels of HbA1C. There was no correlation between the vitreous and serum levels of VEGF or PDGF in patients with PDR. Conclusions: It appears that, in addition to VEGF, PDGF-AA, -AB, and -BB in the vitreous are also correlated with PDR.

Perfluorocarbon liquid utilization in primary vitrectomy repair of retinal detachment with multiple breaks.

Purpose To evaluate the efficacy of pars plana vitrectomy in conjunction with intraoperative perfluoro-n-octane (PFO) use as initial treatment of retinal detachment (RD) with multiple breaks located at various distances from the ora serrata. Methods Twenty-two consecutive eyes (15 phakic, 2 aphakic, and 5 pseudophakic) presenting with RD with multiple breaks and tears underwent primary pars plana vitrectomy, PFO retinal reattachment, transcleral cryopexy or endolaser treatment of breaks, PFO/air exchange, and final injection of 18% perfluoropropane (C3F8). Scleral buckles were not used. The mean follow-up period was 29 months. Results Temporary PFO utilization attached the posterior retina and facilitated the safe removal of vitreous at its base and around the retinal tears. Intraoperative complications included new breaks (3 eyes), enlargement of breaks (2 eyes), and a small bubble of subretinal PFO (1 eye). Postoperatively, the retina remained attached during follow-up in 19 eyes. Cataract developed or progressed in 13 phakic eyes. Conclusions Pars plana vitrectomy in conjunction with intraoperative PFO utilization is effective as initial treatment of RDs with multiple breaks. The main limitation of this technique is the postoperative progressive cataract formation in phakic eyes.

Coats' disease: treatment with intravitreal bevacizumab and laser photocoagulation.

Editor, C oats’ disease is characterized by retinal telangiectasia, macular oedema, exudation and, consequently, exudative retinal detachment. In its advanced stages, it may be complicated by total retinal detachment and glaucoma and may lead to phthisis bulbi (Shields et al. 2001). It usually presents unilaterally in 8–16-year-old males, although it may occur in patients as young as 4 months (Haller 2004). Exudation characterizing Coats’ disease can be attributed to increased vascular permeability caused by telangiectasia and aneurysms in the posterior pole and ⁄or the periphery, facilitating release of vascular endothelial growth factor (VEGF). This growth factor has been shown to cause telangiectasia, microvascular occlusion, microaneurysms, and, consequently, vascular leakage, thus promoting exudation (Sun et al. 2007). Recently, antibodies against VEGF (bevacizumab [Avastin ; Genentech], ranibizumab [Lucentis ; Novartis AG] and pegaptanib [Macugen ; Pfizer, Inc.]) have been employed in managing conditions characterized by exudation, such as age-related macular degeneration (AMD) and diabetic macular oedema (DMO) (Minnella et al. 2007). Corticosteroids have been known to reduce intraocular inflammation, tighten capillary walls and suppress cell proliferation. Intravitreal triamcinolone acetonide has been shown to be useful in increasing visual acuity (VA) in patients with diffuse DMO (Sivaprasad et al. 2006). We describe the management of Coats’ disease in a young adult male, in which laser photocoagulation along with bevacizumab ⁄ triamcinolone intravitreal injection were employed. A 17-year-old male was referred with a severe decrease in VA OD occurring over some weeks. Ophthalmic evaluations included non-standardized Snellen VA, and complete ophthalmic and fundus examination. Active neovascularization in the optic disc and ⁄or elsewhere was confirmed with fluorescein angiography (FA). The patient’s VA OD was 20 ⁄ 1000. Fundus examination revealed considerable exudation involving the posterior pole, and macroaneurysms and telangiectases in the temporal periphery (Fig. 1A). Localized telangiectases in the periphery combined with the overall clinical picture was compatible with Coats’ disease diagnosed in adulthood. These findings were confirmed in FA (Fig. 2A). Treatment

Postoperative Glaucoma Following Infantile Cataract Surgery: An Individual Patient Data Meta-analysis

IMPORTANCE Infantile cataract surgery bears a significant risk for postoperative glaucoma, and no consensus exists on factors that may reduce this risk. OBJECTIVE To assess the effect of primary intraocular lens implantation and timing of surgery on the incidence of postoperative glaucoma. DATA SOURCES We searched multiple databases to July 14, 2013, to identify studies with eligible patients, including PubMed, MEDLINE, EMBASE, ISI Web of Science, Scopus, Central, Google Scholar, Intute, and Tripdata. We also searched abstracts of ophthalmology society meetings. STUDY SELECTION We included studies reporting on postoperative glaucoma in infants undergoing cataract surgery with regular follow-up for at least 1 year. Infants with concurrent ocular anomalies were excluded. DATA EXTRACTION AND SYNTHESIS Authors of eligible studies were invited to contribute individual patient data on infants who met the inclusion criteria. We also performed an aggregate data meta-analysis of published studies that did not contribute to the individual patient data. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Time to glaucoma with the effect of primary implantation, additional postoperative intraocular procedures, and age at surgery. RESULTS Seven centers contributed individual patient data on 470 infants with a median age at surgery of 3.0 months and median follow-up of 6.0 years. Eighty patients (17.0%) developed glaucoma at a median follow-up of 4.3 years. Only 2 of these patients had a pseudophakic eye. The risk for postoperative glaucoma appeared to be lower after primary implantation (hazard ratio [HR], 0.10 [95% CI, 0.01-0.70]; P = .02; I(2) = 34%), higher after surgery at 4 weeks or younger (HR, 2.10 [95% CI, 1.14-3.84]; P = .02; I(2) = 0%), and higher after additional procedures (HR, 2.52 [95% CI, 1.11-5.72]; P = .03; I(2) = 32%). In multivariable analysis, additional procedures independently increased the risk for glaucoma (HR, 2.25 [95% CI, 1.20-4.21]; P = .01), and primary implantation independently reduced it (HR, 0.10 [95% CI, 0.01-0.76]; P = .03). Results were similar in the aggregate data meta-analysis that included data from 10 published articles. CONCLUSIONS AND RELEVANCE Although confounding factors such as size of the eye and surgeon experience are not accounted for in this meta-analysis, the risk for postoperative glaucoma after infantile cataract surgery appears to be influenced by the timing of surgery, primary implantation, and additional intraocular surgery.

Acrylic toric intraocular lens implantation: a single center experience concerning clinical outcomes and postoperative rotation

Purpose: To present clinical results of toric intraocular lens (IOL) implantation for preexisting astigmatism correction and determine the time of any postoperative rotation. Patients and methods: Twenty-nine eyes of 19 patients underwent uncomplicated phacoemulsification and were implanted with an Acrysof

The effect of subconjunctival ranibizumab on primary pterygium: a pilot study.

Purpose: A prospective interventional pilot study was performed to estimate the effect of ranibizumab injection on the clinical and histological picture of primary pterygium. Methods: Five patients with primary pterygia received a single subconjunctival injection of ranibizumab (0.3 mg), whereas 5 nontreated pterygia served as controls. The treated pterygia were surgically removed 3 days, 1 week, 2 weeks, 1 month, and 2 months after the injection, respectively. Digital photographs of the pterygia were taken immediately before injection, 1 week after, and on the day of operation. Results: Ranibizumab was well tolerated by all patients, and no side effects were reported. However, it had no effect on the extent of vascularization of pterygium, regardless of the interval between injection and operation. No regression of pterygium vessels was noted in any of the patients. Immunohistochemical analysis also showed no particular differences in the number of vessels stained positive for vascular endothelial growth factor A, in the intensity of vessel staining among the treated pterygia, and between the treated and the nontreated pterygia. Conclusions: Subconjunctival ranibizumab at a single dose of 0.3 mg was not associated with any side effects but had no effect on the extent of vascularization of primary pterygium in our study.