Fabrizio Giansanti

Corneal endothelial damage after cataract surgery : Microincision versus standard technique

PURPOSE: To compare corneal endothelial changes after phacoemulsification performed with a standard technique versus a bimanual microincision cataract surgery (MICS) technique. SETTING: University ophthalmology department. METHODS: Eighty patients scheduled for routine cataract surgery were randomized into 2 groups; 40 eyes had standard stop‐and‐chop phacoemulsification (standard group) and 40 eyes had stop‐and‐chop phacoemulsification with microincision surgery (MICS group). Central corneal endothelial cell counts, coefficient of variation in cell size, hexagonality, and pachymetry were assessed preoperatively and 1 and 3 months postoperatively. RESULTS: The mean preoperative cell count in the entire sample was 2245 cells/mm2 ± 37 (SE). The mean decreased by 102 cells at 1 month (95% confidence interval [CI], −133 to −71; P<.001) and by 144 cells at 3 months (95% CI, −187 to −102; P<.001). The difference between the standard group and the MICS group was 25 cells at baseline (95% CI, −169 to 120 cells; P = .739), 19 cells at 1 month (95% CI, −163 to 126; P = .799), and 19 cells at 3 months (95% CI, −164 to 125; P = .793). There were no changes in the coefficient of variation or morphology in the overall sample, and the pattern of change did not differ between the 2 groups. Corneal thickness increased by 10.2 μm in the overall sample (95% CI, +4.5 to +16.0; P<.001) and approached baseline values by 3 months with an increase of 3.4 μm (95% CI, −4.1 to 10.8; P = .372). There was no difference in corneal thickness between the groups. CONCLUSION: No significant differences in corneal endothelial cell loss or endothelial morphology were found between MICS and standard incision techniques.

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behçet disease.

Purpose To report a case of posterior uveitis with retinal neovascularization in a patient with Behçet disease treated with infliximab. Methods A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. Results Retinal neovascularization regressed 8 months after the first anti–tumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. Conclusions The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behçet disease.

A Pilot Study on Ocular Safety of Intravitreal Infliximab in a Rabbit Model

PURPOSE To determine whether infliximab may be used safely as an intraocular drug, the ocular safety of intravitreal infliximab in rabbits was studied by clinical examination, electroretinography (ERG), and histology in rabbits. METHODS Twelve New Zealand albino rabbits were selected for this study. Different infliximab doses, namely 1.0 mg, 1.7 mg, and 3.3 mg in 0.1 mL, were injected intravitreally into one eye each of three rabbits. As a control, the vehicle solution was injected into the fellow eye of each animal. Eye clinical examination and ERG recordings were made before and 2, 6, and 12 weeks after injection. Eventually, the rabbits were humanely killed, and the retinas were examined by light microscopy. In addition, the elimination half-life of the drug in the vitreous was assessed. RESULTS Slit lamp biomicroscopy, indirect funduscopy, and ERG evidenced no significant differences between control and infliximab-injected eyes in this rabbit model, at any of the tested doses. Histologic examination revealed no retinal abnormality in the rabbits injected with 1 mg and 1.7 mg intravitreal infliximab. In two of three eyes injected with 3.3 mg infliximab, significant edema of the nerve fibers was detected compared with the control group. The half-life of the drug was estimated to be 8.5 days. CONCLUSIONS These results indicate that infliximab may be a safe intravitreal drug in the rabbit model at a dose of up to 1.7 mg. If proven safe and efficacious in further studies, intravitreal injection of infliximab could be considered an alternative to systemic administration in selected patients.

Intravitreal bevacizumab therapy for choroidal neovascularization secondary to age-related macular degeneration : 6-month results of an open-label uncontrolled clinical study

Purpose To investigate the 6-month safety and clinical outcomes of intravitreal injections of bevacizumab administered to treat choroidal neovascularization secondary to age-related macular degeneration. Methods Twenty-seven patients underwent 1.25 mg intravitreal injections of bevacizumab at baseline. A similar intravitreal injection was administered to all eyes at 1 and 2 month follow-up visits. At baseline and at each follow-up visit (1, 2, 3, and 6 months), patients underwent best-corrected visual acuity (BCVA) measurement, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Laboratory testing, visual field analyses, and endothelial cell counts were performed at baseline and third and sixth months. Results At 3 months, the mean BCVA remained substantially stable at 20/100. Mean central retinal thickness (CRT) decreased from 373 to 279 μm (p<0.01). Mean lesion greatest linear dimension (GLD) decreased from 4087 to 3782 microns (p<0.01). At 6 months, mean BCVA slightly decreased from 20/100−1 to 20/125−3 (not significant, p=0.40). Mean CRT was still inferior to baseline (305 μm, p<0.01). Mean lesion GLD was 4186 μm, not different from baseline values (p=0.59), but superior to 3-month mean GLD (p<0.01). Significant visual field defects or endothelial cell losses were not detected at 3 and 6 months. Laboratory testing did not reveal any clinically significant deviations compared to baseline values. Conclusions Intravitreal therapy using bevacizumab over 6 months showed stabilization of visual acuity and choroidal neovascularization activity; the safety data were convincing. (Eur J Ophthalmol 2007; 17: 230–7)

Photodynamic therapy for choroidal neovascularization in pediatric patients

Purpose: To report the use of photodynamic therapy (PDT) for choroidal neovascularization (CNV) in pediatric patients. Methods: Five patients (age range, 7–15 years) who underwent PDT for idiopathic CNV (n = 2) or CNV secondary to macular toxoplasmic scar (n = 3) were included in this study. Follow-up ranged from 12 months to 18 months. PDT was performed according to the standard protocol. We evaluated visual acuity, fluorescein leakage from the CNV, greatest linear dimension of the lesion, and occurrence of ocular or systemic adverse events at baseline and during follow-up. Results: No severe or moderate visual loss occurred in all cases during follow-up. PDT reduced CNV leakage in four cases. No serious ocular or systemic adverse events were recorded. Retinal pigment epithelium atrophic changes were observed around the regressed CNV, but they did not appear to cause visual loss. Conclusions: PDT was safe for pediatric patients, and visual acuity was substantially stable after one or few treatments. Further follow-up is needed to assess if retinal pigment epithelium atrophic changes around the regressed CNV, possibly related to PDT, could affect vision in the long term.

Lipid-polyethylene glycol based nano-ocular formulation of ketoconazole.

Ophthalmic mycoses including corneal keratitis or endophthalmitis affects 6-million persons/year and can cause blindness. Its management requires antifungals to penetrate the ocular tissue. Oral use of Ketoconazole (KTZ), the first broad-spectrum antifungal to be marketed, is now restricted to life-threatening infections due to severe adverse effects and drug-interactions. Local use of KTZ loaded nanocarrier system can address its toxicity, poor solubility, photodegradation, permeation and bioavailability issues. Solid lipid nanoparticles (SLNs) comprising Compritol(®) 888 ATO and PEG 600 matrix, were presently prepared using hot high-pressure homogenization. Employing extensive characterization: TEM, NMR, DSC, XRD and FTIR, it is proposed that SLNs comprise of a polyethylene glycol (PEG) core into which KTZ is dissolved. PEG endows the lipid matrix with amorphousness and imperfections; rigidity; and, stability to aggregation, on storage and autoclaving. PEG is a simple, cost-effective and safe polymer with superior solubilizing and surfactant-supporting properties. Without its inclusion KTZ could not be loaded into SLNs. It ensured high incorporation efficiency (70%) of KTZ; small size (126 nm); and, better permeation into the eye. Pharmacokinetic studies indicated 2.5 and 1.6 fold higher bioavailability (AUC) in aqueous and vitreous humor, respectively. Biocompatibility and in vitro (both in corneal and retinal cell lines) and in vivo (in rabbits) ocular safety is the other highlight of developed formulation.

Intravitreal bevacizumab (Avastin) for choroidal neovascularization in angioid streaks: a case series.

Background: Intravitreal (IV) bevacizumab (Avastin®, Roche), initially used for the off-label treatment of neovascular age-related macular degeneration (AMD), has extended itself to treat various ocular pathologies such as choroidal neovascularization not associated to AMD. Methods: IV bevacizumab 1,25 mg (Avastin) was used in the treatment of choroidal neovascularization (CNV) in 6 eyes of 5 patients with angioid streaks. All cases had a history of photodynamic treatment (PDT) or laser treatment and all showed progressive worsening despite the use of these therapies. Results: After injection patients were followed up at nearly 2-month intervals. IV Avastin was repeated in case of recurrence. Three eyes were treated combining PDT and IV Avastin. Cases were followed up for 7–14 months. All patients needed more IV injections. Five out of 6 eyes showed an improvement of BCVA and a slight reduction of leakage and size with FA. Conclusion: This small series suggests that IV Avastin might be useful in the treatment of CNV due to AS.

Long-term results of photodynamic therapy for subfoveal choroidal neovascularization with pathologic myopia.

Purpose: The purpose of our study was to determine the long-term visual and anatomic outcomes of photodynamic therapy in patients affected with choroidal neovascularization secondary to pathologic myopia. Methods: We retrospectively evaluated 43 eyes of 43 patients. Patients with pathologic myopia were included if they had received photodynamic therapy for choroidal neovascularization involving the center of the avascular foveal zone and if they had a follow-up of at least 5 years. We included only the cases for which both of the examiners of the FAs were in agreement concerning the subfoveal localization of choroidal neovascularization. Patients treated with other therapies such as anti–vascular endothelial growth factor or steroids in the study eye were excluded. Visual acuity was measured using Early Treatment Diabetic Retinopathy Study charts. Anatomic outcome measures were the lesion size expressed as the greatest linear diameter and the chorioretinal atrophy that developed around the regressed choroidal neovascularization. Results: Average visual acuity was stable during the first year, tended to be worse at 2 years, whereas it was significantly worse at 3 years and afterward, reaching a loss of nearly 3 lines at 7 years. We found that neither the number of photodynamic therapy treatments nor baseline photodynamic therapy spot size influenced change of visual acuity during follow-up. Chorioretinal atrophy around choroidal neovascularization was detected in 83% of patients at the 5-year follow-up visit. Conclusion: The results showed that visual acuity decreased significantly after a long follow-up period mainly because of the development of chorioretinal atrophy.

Intravitreal Infliximab Clearance in a Rabbit Model: Different Sampling Methods and Assay Techniques

PURPOSE To investigate the clearance of intravitreal infliximab with the use of different sampling techniques and immunoassay methods in rabbits. METHODS Infliximab (1.6 mg) was intravitreally injected into both eyes of 47 rabbits. Two approaches were used to collect the vitreous: the classic method and a microsampling technique. Whereas the classic method consists of collection of the whole vitreous after enucleation, the microsampling technique consisted of the aspiration of small (10-15 microL) samples with a 200-microL syringe. Samples were taken from 30 minutes to 40 days using both methods and were then compared. Infliximab concentration was estimated with competitive ELISA, dot blot analysis, and Western blot analysis. RESULTS The vitreous half-life of infliximab was estimated to be 6.5 +/- 0.6 days. The data indicated monoexponential decay reaching its conclusion after approximately 40 days. This decay was preceded by 4-day-long diffusion in the vitreous. Microsampling proved to be effective in the vitreous collection, giving statistically comparable signals (+/- 4%, P = 0.68) with respect to the classic procedure. ELISA proved to be the best analytical technique--especially if coupled with microsamplings--because of its lower detection limit, precision, and reduced amount of sample needed. No differences were observed between half-life values obtained by ELISA and dot blot analysis (P = 0.081) and Western blot analysis (P = 0.614). CONCLUSIONS The findings of this study added to the knowledge of infliximab clearance in the vitreous and confirmed the validity of a microsampling technique that was compared with the classic one. ELISA was found to be the best analytical technique when using microsampling.

Photodynamic therapy using methyl aminolevulinate acid in eyelid basal cell carcinoma: a 5-year follow-up study.

Purpose: To evaluate retrospectively the long-term results of methyl aminolevulinate photodynamic therapy for the treatment of eyelid basal cell carcinoma. Methods: Sixteen consecutive patients with eyelid basal cell carcinoma were treated with methyl aminolevulinate photodynamic therapy between January 2002 and April 2003. Selection criteria were tumors located at least 3 mm from the tarsus, surgery not indicated because of poor general health, and recurrences with unclear location definition. Patients were treated with an 80-J cm2 light-emitting diode light source (632 nm) after topical application of methyl aminolevulinate cream and occlusion for 4 hours. Data were available for follow-up at day 1, week 1, month 1, and every 6 months for 5 years. Results: The mean number of photodynamic therapy session per patient was 3.1 (range, 2–6) Complete clinical recovery was observed after the 5-year follow-up in 13 of 16 patients (82%). Two patients did not respond at all to treatment and 1 patient presented with recurrence after 3 years of tumor-free follow-up. Tolerance of treatment was good with few side effects. Conclusions: The absence of complications, good tolerance, and a notable success rate make this nonsurgical procedure promising for the treatment of basal cell carcinoma of the eyelid in selected patients.