Flavia Chiosi

Low fluence rate photodynamic therapy combined with intravitreal bevacizumab for neovascular age related macular degeneration.

Aims To report the efficacy and safety of intravitreal bevacizumab (IVB) alone versus IVB plus low-fluence photodynamic therapy (PDT) in age-related macular degeneration (AMD) patients and to verify the occurrence of a synergistic effect of the combined approach on visual acuity, size and morphology of lesion, as well as on the treatment rate. Method Prospective comparative interventional study on 85 patients with treatment-naive classic, or predominantly classic, subfoveal choroidal neovascularisation secondary to AMD. Patients were randomly assigned to group 1 (IVB injections) and group 2 (IVB plus low fluence PDT). In group 2, the PDT with verteporfin was delivered with a low fluence rate (300 mW/cm2 for 83 s, 25 J/cm2). The follow-up was scheduled at 1, 3, 6, 9 and 12 months. Results The eye without recurrence received a mean of 2.8 (group 1) versus 1.4 (group 2) IVB injections, whereas the eyes with recurrence received a mean of 3.2 (group 1) versus 2.2 (group 2) IVB injections. The difference in reinjection rate between the two groups was statistically significant (p=0.03, ANOVA test). Visual acuity improvement was not statistically significant between the two groups (p=0.31). Conclusion The combination of IVB with low fluence PDT for the treatment of classic or predominantly classic neovascular AMD works in a synergistic fashion with a significant reduction in IVB reinjections rate.

Intravitreal pegaptanib sodium (Macugen®) for treatment of diabetic macular oedema: a morphologic and functional study.

AIMS To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes. METHODS A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections. RESULTS Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported. CONCLUSIONS Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO.

Intravitreal pegaptanib sodium (Macugen) for treatment of myopic choroidal neovascularization: a morphologic and functional study.

Background: To report the morphologic and functional outcomes resulting from the use of intravitreal pegaptanib (IVP) sodium (Macugen) in patients with myopic choroidal neovascularization. Methods: An open-label, nonrandomized, prospective clinical trial was performed. Morphologic outcome, such as foveal thickness, was assessed by optical coherence tomography, whereas functional outcomes were assessed by best-corrected visual acuity and microperimetry. Treatment protocol consisted of 3 consecutive IVP (0.3 mg/0.05 mL; baseline, 6th week, and 12th week). Follow-up checks were scheduled at the following intervals: baseline, 18, 24, 36, and 48 weeks. Results: Twenty eyes from 20 patients were studied. All patients completed follow-up at 48 weeks. After IVP, a significant decrease in foveal thickness occurred (−20%), and at the end of follow-up, choroidal neovascularization closure was obtained in all eyes. An improvement of functional parameters was recorded in all patients (best-corrected visual acuity from 25.5 ± 8.09 letters to 45.5 ± 8.16 letters, P < 0.0001; microperimetry from 8.40 ± 2.14 dB to 10.8 ± 2.05 dB, P < 0.01). The mean number of IVP was 3, and none of patients met the re-treatment criterion during the entire follow-up period. Neither ocular nor systemic side effects were observed. Conclusion: The findings demonstrate that the selective inhibition of VEGF-165 isoform by IVP is an effective treatment for myopic choroidal neovascularization.

Ocular manifestations in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): A case-series

Background: Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is an autosomal dominant vascular disorder characterized by severe and recurrent nosebleeds, muco-cutaneous telangiectasias, and, in some cases, life-threatening visceral arteriovenous malformations. Ocular abnormalities include conjunctival telangiectasia, arteriovenous fistula, angiectasia, phlebectasia, and angioma. Material and Methods: We describe the ocular abnormalities in 8 patients from a pedigree with hereditary hemorrhagic telangiectasia. This article also reviews and discusses the relevant literature. Results: Five patients (62.5%) had conjunctival telangiectasias and 3 (37.5%) retinal abnormalities, consisting mainly of choriocapillaris atrophy. Conclusions: To the best of our knowledge, this is the first report describing the occurrence of choriocapillaris atrophy in patients affected by hereditary hemorrhagic telangiectasia and belonging to the same pedigree.

Treatment of Exudative Age-Related Macular Degeneration with Ranibizumab Combined with Ketorolac Eyedrops or Photodynamic Therapy

Purpose: To evaluate whether ketorolac eyedrops plus intravitreal ranibizumab (IVR) or verteporfin photodynamic therapy plus IVR provides additional benefit over IVR monotherapy for treatment of choroidal neovascularization in age-related macular degeneration. Methods: This was a prospective, randomized, pilot study in 75 patients with naive choroidal neovascularization. Patients were randomized 1:1:1 into 3 groups: ranibizumab monotherapy (RM), ranibizumab plus ketorolac, or ranibizumab plus loading-phase reduced-fluence verteporfin photodynamic therapy (RV) groups. Results: At 12 months, all groups showed significant improvement in both best-corrected visual acuity and central retinal thickness. The mean best-corrected visual acuity change from baseline to 12 months was −0.14 ± 0.52 logMAR (20/73 ± 20/29), −0.25 ± 0.60 logMAR (20/46 ± 20/27), and −0.10 ± 0.30 (20/97 ± 20/40) logMAR in RM, ranibizumab plus ketorolac, and RV groups, respectively. The mean central retinal thickness change from baseline to 12 months was −125 ± 15 &mgr;m, −141 ± 21 &mgr;m, and −130 ± 15 &mgr;m in RM, ranibizumab plus ketorolac, and RV groups, respectively. Both ranibizumab plus ketorolac and RV groups required fewer IVR treatments than RM. Conclusion: Compared with RM and ranibizumab plus verteporfin photodynamic therapy, the combination of 0.45% ketorolac eyedrops 3 times a day and ranibizumab in patients with choroidal neovascularization provided superior best-corrected visual acuity and central retinal thickness outcomes. Both combination regimens required fewer IVR injections than RM during the 12-month follow-up period.

Resolvins and aliamides: Lipid autacoids in ophthalmology – What promise do they hold?

Resolvins are a novel class of lipid-derived endogenous molecules (autacoids) with potent immunomodulating properties, which regulate the resolution phase of an active immune response. These modulating factors are locally produced, influencing the function of cells and/or tissues, which are produced on demand and subsequently metabolized in the same cells and/or tissues. This review is focused on certain lipid autacoids with putative relevance for ophthalmology in general and for dry eye more specifically. We also briefly investigate the concept of aliamides and the role of palmitoylethanolamide in ophthalmology, and analyze in more detail the putative role and the preclinical and clinical development of resolvins as emerging treatments for dry eye and related disorders, with a focus on one of the lead resolvin derivatives – RX-10045.

Retinal phototoxicity induced by hydrochlorothiazide after exposure to a UV tanning device.

UV radiation is known to cause acute and chronic eye and skin damage. The present case report describes the occurrence of hydrochlorothiazide‐induced retinal phototoxicity immediately after exposure to UV light emanated from a sunbed in a 40‐year‐old myopic woman. During the tanning session she had always worn UV protective eyewear, except for a few minutes when she took the protective goggles off to put her spectacles on to locate and turn the timer switch off. At baseline her visual acuity was 10/25 in OD and 10/80 in OS. Fundus examination revealed the presence of retinal lesions in both eyes. More specific tests confirmed the presence of a phototoxic macular damage. Hydrochlorothiazide was discontinued, and she was recommended to wear UV filtering glasses. Over the follow‐up period (12 months), a slow and progressive visual acuity recovery in both eyes occurred. At the last check the visual acuity improvement was of about 60% from baseline in both eyes. Fundus examination showed only a juxtafoveal flat pigmented scar of the retinal pigment epithelium in both eyes, milder in OD. The constant rise in the number of sunbed users makes the knowledge of UV‐related side effects a problem that cannot be postponed further. Awareness of the general public about the harmful effects of UV exposure must represent one of the leading preventive health strategies. Therefore, a careful analysis of the medical history before the admission to a sunbed session throughout a questionnaire could represent an economic and effective measure to avoid further cases of a phototoxic macular damage in patients taking photosensitizing compounds.

Cytoprotective Effects of Citicoline and Homotaurine against Glutamate and High Glucose Neurotoxicity in Primary Cultured Retinal Cells

Citicoline and homotaurine are renowned compounds that exhibit potent neuroprotective activities through distinct molecular mechanisms. The present study was undertaken to demonstrate whether cotreatment with citicoline and homotaurine affects cell survival in primary retinal cultures under experimental conditions simulating retinal neurodegeneration. Primary cultures were obtained from the retina of fetal rats and exposed to citicoline plus homotaurine (100 μM). Subsequently, neurotoxicity was induced using excitotoxic levels of glutamate and high glucose concentrations. The effects on retinal cultures were assessed by cell viability and immunodetection of apoptotic oligonucleosomes. The results showed that a combination of citicoline and homotaurine synergistically decreases proapoptotic effects associated with glutamate- and high glucose-treated retinal cultures. This study provides an insight into the potential application of citicoline and homotaurine as a valuable tool to exert neuroprotective effects against retinal damage.