Massimo Nicolò

Retinal pigment epithelial tear following intravitreal injection of bevacizumab (Avastin).

PURPOSE To report one case of retinal pigment epithelium tear following intravitreal bevacizumab injection for neovascular age-related macular degeneration. METHODS A 59-year-old patient presented with occult choroidal neovascularization associated with a serous pigment epithelial detachment secondary to age-related macular degeneration. The patient was treated with an intravitreal injection of bevacizumab. RESULTS The patient developed a retinal pigment epithelium tear 60 days following the intravitreal injection. CONCLUSIONS This report describes the development of retinal pigment epithelium tear after intravitreal bevacizumab injection. Future studies should be performed to evaluate which subtypes of lesions are most susceptible to this potential devastating visual complication.

Occult with no classic choroidal neovascularization secondary to age-related macular degeneration treated by intravitreal triamcinolone and photodynamic therapy with verteporfin.

Purpose: To examine combined treatment with intravitreal triamcinolone acetonide (IVT) and photodynamic therapy (PDT) for occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration. Methods: In this prospective, interventional case series, 11 eyes of 10 consecutive patients with occult with no classic CNV underwent a single injection (25 mg) of IVT followed 1 month later by PDT. Best-corrected visual acuity was measured by Early Treatment Diabetic Retinopathy Study (ETDRS) protocol refraction. Results: Median best-corrected visual acuity was 20/160, 20/80, 20/80, 20/50, and 20/80 at baseline and 1, 3, 6, and 12 months, respectively. Best-corrected visual acuity at baseline was statistically different (P < 0.05) than best-corrected visual acuity at 1, 3, and 6 months. Of 11 eyes, 5 (45.5%), 7 (63.6%), 7 (63.6%), and 4 (36.3%) had improved best-corrected visual acuity of at least 3 ETDRS lines at 1, 3, 6, and 12 months, respectively, while 6 (54.5%), 9 (81.8%), 10 (91%), and 8 (73%) had improved best-corrected visual acuity of at least 2 ETDRS lines at 1, 3, 6, and 12 months, respectively. Two eyes (18%) lost >3 lines at 12 months. One eye had intraocular hypertension at 3 months and was treated with a combination of topical antiglaucomatous drugs. One eye developed a dense cataract at the last follow-up visit. No endophthalmitis, retinal detachment, or vitreous hemorrhage developed. Fluorescein leakage and retinal thickness reduced significantly after treatment. Conclusions: Improvement of best-corrected visual acuity and lack of fluorescein leakage suggest combination treatment with IVT and PDT for occult with no classic CNV merits further investigation.

Association Between the Efficacy of Half-Dose Photodynamic Therapy With Indocyanine Green Angiography and Optical Coherence Tomography Findings in the Treatment of Central Serous Chorioretinopathy

PURPOSE To determine the efficacy of half-dose photodynamic therapy (PDT) in relation to indocyanine green angiography (ICGA) and optical coherence tomography (OCT) findings for treating chronic central serous chorioretinopathy (CSC). DESIGN Observational case series. METHODS Thirty-eight eyes of 37 patients with chronic CSC and symptoms for at least 6 months were recruited. PDT was performed using half the normal dose of verteporfin. A total light energy of 50 J/cm(2) over 83 seconds was delivered to the area of choroidal hyperfluorescence as observed on ICGA. The resolution of the subretinal fluid and recurrence rates were assessed in relation to the different degrees of choroidal hyperfluorescence and the distribution of fluid in the neuroepithelium, namely subretinal fluid or posterior retinal cystoid degeneration. RESULTS After half-dose PDT a dry macula was obtained in 86.8% and 92.1% of the eyes at 1 month and at the last follow-up (14.2 ± 5.8 months) respectively. ICGA at baseline showed intermediate and intense hyperfluorescence in 39.4% and 60.5% of the eyes respectively. All eyes with intermediate hyperfluorescence had only subretinal fluid at OCT and a dry macula was obtained in 87% and 100% at 1 month and at the last follow-up after half-dose PDT. In the intense hyperfluorescence group, 82.6% and 17.4% of the eyes had subretinal fluid only or both subretinal fluid and posterior retinal cystoid degeneration respectively. In the intense hyperfluorescence group with subretinal fluid only, a dry macula was obtained in 89.5% and 100% of the eyes at 1 month and at the last follow-up respectively. In the intense hyperfluorescence group with both subretinal fluid and posterior retinal cystoid degeneration, a dry macula was obtained in 75% and 25% of the eyes at 1 month and at the last follow-up respectively. Overall, of the 23 eyes with intense hyperfluorescence, 20 eyes (87%) had a dry macula starting from 1 month for the entire follow-up period. CONCLUSION The half-dose PDT success rate in eyes with chronic CSC depends also on the distribution of fluid in the neuroepithelium. Half-dose PDT might not be effective or the recurrence rate might be high in eyes with posterior retinal cystoid degeneration.

Retinal angiomatous proliferation treated by intravitreal triamcinolone and photodynamic therapy with verteporfin

PurposeTo examine combined treatment of intravitreal triamcinolone acetonide (IVT) and photodynamic therapy (PDT) for retinal angiomatous proliferation (RAP).MethodsTen eyes of eight consecutive patients with RAP underwent a single injection (about 20 mg) of IVT followed 1 month later by PDT. Best-corrected visual acuity (BCVA) was measured by standardized protocol refraction.ResultsMedian BCVA was 20/160, 20/64, 20/98, 20/89, 20/89, 20/125 at baseline and 1, 3, 6, 9 and 12 months, respectively. Of ten eyes, six (60%) improved BCVA of at least 3 lines at 1, 3, 6 and 9 months. Four (40%) eyes improved BCVA of at least 3 lines at 12 months. Three eyes (30%) lost >3 lines at 12 months. In all patients intraocular pressure was well controlled. No endophthalmitis, retinal detachment or vitreous haemorrhage developed.ConclusionsImprovement of BCVA suggests that combination treatment with IVT and PDT for RAP merits further investigation.

Intravitreal triamcinolone in the treatment of serous pigment epithelial detachment and occult choroidal neovascularization secondary to age-related macular degeneration

Purpose To report two cases of occult choroidal neovascularization (CNV) and serous pigment epithelial detachment (PED) treated with intravitreal triamcinolone (IVT) injections. Methods Interventional case reports. Results Both patients showed an increase in visual acuity and a complete flattening of the PED at 10 months (Case 1) and 4 months (Case 2) after IVT injections. No complications or adverse effects are reported. Conclusions Future studies should be designed to investigate if IVT can effectively influence the clinical and functional outcome of eyes with serous PED and occult CNV secondary to age-related macular degeneration, for which at the moment no treatment has been shown to be effective.

Branch retinal artery occlusion combined with branch retinal vein occlusion in a patient with hepatitis C treated with interferon and ribavirin.

Purpose To report a case of a combined branch retinal artery and vein occlusion in a patient with hepatitis C treated with interferon and ribavirin. Methods A 29-year-old man with a 1-week history of sudden visual field defect and decrease of central visual acuity was examined. Results Ophthalmoscopy and fluorescein angiography demonstrated an ischemic whitening of the inferior hemi-retina involving part of the macular region, numerous intraretinal hemorrhages, and a significant delay in arterial and vein filling of the dye. Conclusions The findings of a retinopathy associated with interferon and ribavirin treatment of hepatitis C are important. The symptomatic permanent visual field defect and decrease of central visual acuity developing following a branch retinal artery and vein occlusion event emphasizes the need for careful and regular ocular monitoring of patients receiving interferon for hepatitis C.

Detection of tenascin-C in surgically excised choroidal neovascular membranes

Abstract · Background: Increase of tenascin-C (TN-C) expression has been found in pathologic tissues in which angiogenesis occurs. The aim of this study was to investigate TN-C expression in human choroidal neovascularization (CNV). · Methods: Ten choroidal neovascular membranes were surgically removed from 10 patients with age- related macular degeneration (n=6) and multifocal choroiditis (n=4). All membranes underwent immunohistochemical evaluation using monoclonal antibodies against TN-C and factor VIII. · Results: All membranes were positive for TN-C, which was abundantly and diffusely expressed in the extracellular matrix. · Conclusions: Our results support the concept that TN-C has a role in cell proliferation and neovascularization in humans. TN-C, as a marker of angiogenesis, may provide novel rationales for the development of pharmacologic therapies for neovascular disorders, particularly CNV.

Ranibizumab for Visual Impairment due to Diabetic Macular Edema: Real-World Evidence in the Italian Population (PRIDE Study)

Purpose. An expanded access program (PRIDE study) in Italy to provide ranibizumab 0.5 mg to diabetic macular edema (DME) patients, prior to reimbursement. Methods. Open-label, prospective, phase IIIb study. Majority of patients were not treatment-naïve before enrollment. Patients received ranibizumab as per the EU label (2011). Safety was assessed by incidences of ocular/systemic adverse events (AEs) and serious AEs (SAEs) and efficacy in terms of visual acuity (VA) change from baseline (decimal score or Snellen (20/value)). Results. Overall, 515 patients (83.5%) completed the study. In unilateral/bilateral patients, commonly observed AEs were cardiac disorders (1.3%/1.3%) and nervous system disorders (1.3%/1.1%); SAEs were reported in 4.5%/4.8% of patients. Acute renal failure, lung carcinoma, and cardiac arrest were the causes of death in one unilateral and two bilateral patients. Ranibizumab improved/maintained VA (Snellen (20/value)/decimal scores) in both unilateral (up to −16.7/1.5) and bilateral patients (up to −23.6/1.2) at Month 5, with a mean of 4.15 and 4.40 injections, respectively. Overall, no difference was observed in the VA outcomes and treatment exposure between unilateral/bilateral patients. Conclusions. The PRIDE study provided early ranibizumab access to >600 Italian patients. Ranibizumab was well-tolerated and improved/maintained VA in 40.2%–68.8% patients, with no differences in case of unilateral or bilateral pathology. The study is registered with EudraCT.

Marker Gene Transfer and Oncolysis of Human Y79 Retinoblastoma Cells Mediated by Herpes simplex Virus Mutants

Three different herpes simplex virus (HSV) mutants, designated hrR3, MGH-1 and R3616, were used to infect Y79 retinoblastoma cells grown in suspension. Two parameters were assayed: (a) vector-mediated gene expression, measured by histochemical staining of a transferred LacZ transgene, and (b) virus-mediated oncolysis, determined by the inability of infected cells to exclude trypan blue dye. The tested HSV mutants were found to infect cells grown in suspension at a relatively low multiplicity of infection (MOI = 0.01) and were capable of transferring the LacZ gene as early as 2 days after infection. Furthermore, differences in oncolytic activity were observed amongst the tested viruses: MGH-1 and R3616 exhibited 50% cell kill at a MOI of 0.1 over a period of 6 days, whereas hrR3-mediated oncolysis appeared less efficient. These studies provide a rationale for further exploitation of oncolytic herpes viruses as a potential treatment of intraocular tumors.

Intravitreal triamcinolone acetonide as primary treatment for diffuse diabetic macular edema: a prospective noncomparative interventional case series.

Purpose To evaluate the efficacy and safety of one intravitreal injection of 25 mg of triamcinolone acetonide as primary treatment for diffuse diabetic macular edema. Methods Intravitreal triamcinolone acetonide injection was performed in 30 eyes with previously untreated diabetic macular edema. The main outcome measures were logMAR visual acuity (VA) and central macular thickness (CMT) at 1, 3, and 6 months. A secondary outcome was intraocular pressure progression. Results Visual acuity results for 30 eyes that had a follow-up of at least 6 months are presented. Twenty of them were followed up to 10.1 ±2.38 months. Preoperatively, VA was 0.54±0.27. At 1, 3, and 6 months follow-up, VA was 0.44±0.29 (p=0.001), 0.43±0.28 (p=0.001), and 0.45±0.29 (p=0.006), respectively. Preoperatively, CMT was 417.3±143.5 μm. At 1, 3, and 6 months follow-up, CMT was 277.3 +74.0 μm (p<0.0001), 279.6±94.4 μm (p<0.0001), and 297.07±114.87 μm (p=0.002), respectively. For the 20 eyes with a follow-up of 10.1±2.38 months, VA was 0.5±0.25 and 0.50±0.32 at baseline and at the last follow-up visit, respectively (p>0.05). Preoperatively, intraocular pressue (IOP) was 15.13±1.48 mmHg. IOP was 18.26±2.71 mmHg, 20.07±4.27 mmHg, and 20.4±6.18 mmHg, at 1, 3, and 6 months, respectively (p<0.0001). Four eyes underwent uncomplicated filtrating surgery for intractable glaucoma. Conclusions Intravitreal triamcinolone as primary treatment effectively increases VA and reduces CMT due to diffuse diabetic macular edema. Longer follow-up and randomized clinical trial are war ranted. Safety results highlight the need to further study the relationship between triamcinolone and intraocular pressure.