Enrico Peiretti

Rebound macular edema following bevacizumab (Avastin) therapy for retinal venous occlusive disease.

Background: Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), has been given via intravitreal injection as an off-label therapy for both neovascular age-related macular degeneration and for macular edema secondary to retinal vascular disease. The authors describe three patients with macular edema secondary to retinal venous occlusion whose edema initially responded to intravitreal bevacizumab but subsequently recurred in excess of that observed before treatment. Methods: This is a retrospective case series of three patients with macular edema secondary to retinal vein occlusion treated with intravitreal bevacizumab. Results: In all three patients, the rebound retinal edema observed was more pronounced than that present before treatment. Conclusion: These cases suggest a potential limitation of using relatively short-acting VEGF antagonists in retinal vascular disease of a chronic nature. Frequent repeated injections may be required to prevent a rebound effect with no clearly defined endpoint. Until the long-term safety of multiple injections of these agents is established, the authors recommend caution in using this treatment strategy.

Acute central serous chorioretinopathy and fundus autofluorescence

Objectives: To describe fundus autofluorescence (FAF) in a series of patients with acute central serous chorioretinopathy (CSC). Methods: Nine eyes of six patients with acute CSC were evaluated with fluorescein angiography (FA) and FAF imaging to evaluate the nature of the focal retinal pigment epithelial (RPE) leak evident with FA. Results: All nine eyes in this series demonstrated hypoautofluorescence corresponding precisely to the site of the focal RPE leak seen on FA. Conclusions: In this group of patients, the acute focal RPE leaks seen with FA corresponded precisely to an area of hypoautofluorescence imaged with FAF. This observation supports the concept that a mechanical defect or absence of the RPE accounts for the leakage from the inner choroid to the subneurosensory space in CSC. FAF is also a useful noninvasive diagnostic adjunct to identify the focal RPE leak in patients with acute CSC.

Photodynamic therapy of corneal neovascularization with verteporfin

Purpose. To describe the effect of photodynamic therapy (PDT) using verteporfin (Visudyne®) on corneal neovascularization (CNV) in two patients. Methods. Two patients with corneal neovascularization were treated with a nonthermal laser light at 689 nm delivered 15 min after an intravenous infusion of verteporfin. Postoperative outcome of neovascularization was followed clinically (inflammation, intraocular pressure, and visual acuity) and photographically [color photographs and corneal fluorescein and indocyanine green (ICG) angiography] for a minimum of 6 months. Results. Successful photothrombosis of corneal neovascularization was obtained immediately after treatment in the two patients, and regression was verified by corneal fluorescein and ICG angiography. In one case, partial vessel recanalization was observed after 1 month, and treatment was repeated, with complete regression of new vessels. No relevant side effects were observed in our cases. Conclusions. PDT with verteporfin is an effective and safe procedure indicated for patients with corneal neovascularization; however, multiple sessions may be required.

Intravitreal bevacizumab as a treatment for choroidal neovascularisation secondary to myopia: 4-year study results

OBJECTIVES To report long-term follow-up results from intravitreal bevacizumab (IVB) treatment of choroidal neovascularisation (CNV) secondary to pathologic myopia (PM). DESIGN The study was designed as a retrospective analysis of consecutive patients presenting with PM. PARTICIPANTS Twenty-one eyes were examined from 20 different patients. METHODS The study was designed as a retrospective, consecutive, nonrandomised, interventional case series. Twenty-one eyes from 20 patients with CNV secondary to PM who were treated with bevacizumab were followed for a maximum of 52 months. Best-corrected visual acuity (BCVA), optical coherence tomography, and fluorescein and indocyanine green angiography were performed on each patient at baseline presentation and every 3 months thereafter for the entire follow-up period. The continuation therapy was based on dosing as needed regimen (PRN) for treatment assessment. RESULTS Overall, 15 (71.4%) of the 21 eyes studied demonstrated an improvement of ≥ 1 line on the Snellen chart. A total of 3 (14.3%) eyes showed no change with this analysis, and 3 (14.3%) eyes lost 1 line of discrimination. After the 4-year study period, fluorescein angiography suggested absence of angiographic leakage or fibrotic lesions in 15 eyes, and 3 eyes showed partial regression of myopic CNV. The remaining 3 eyes demonstrated total regression of CNV. CONCLUSIONS Intravitreal bevacizumab appears to be an effective therapy for myopic CNV and its benefit may persist in a long-term follow-up, on the basis of PRN treatment compared to the natural history of the disease.

CHOROIDAL NEOVASCULARIZATION IN CAUCASIAN PATIENTS WITH LONGSTANDING CENTRAL SEROUS CHORIORETINOPATHY.

Purpose: To report the frequency of choroidal neovascularization (CNV) in Caucasian patients with chronic central serous chorioretinopathy (CSC). Methods: Retrospective consecutive series of 272 eyes (136 patients) who were diagnosed as having chronic CSC based on clinical and multimodal fundus imaging findings and documented disease activity for at least 6 months. The CNVs were mainly determined by indocyanine-green angiography. Results: Patients were evaluated and followed for a maximum of 6 years, with an average follow-up of 14 ± 12 months. Distinct CNV was identified in 41 eyes (34 patients). Based on fluorescein angiography, 37 eyes showed occult with no classic CNV, 3 eyes showed predominantly classic and 1 eye had a disciform CNV. Furthermore, indocyanine-green angiography revealed polypoidal choroidal vasculopathy lesions, in 27 of the 37 eyes, classified as occult CNV on fluorescein angiography. In total, 17.6% of our patients with chronic CSC were found to have CNV that upon indocyanine-green angiography were recognized as being polypoidal choroidal vasculopathy. Conclusion: In our series of Caucasian patients, we found a significant correlation between chronic CSC and CNV, in which the majority of patients with CNV were found to have polypoidal choroidal vasculopathy. Our findings suggest that indocyanine-green angiography is an indispensable tool in the investigation of chronic CSC.

Unilateral retinitis pigmentosa: a proposal of genetic pathogenic mechanisms.

Purpose To investigate and integrate anatomic and physiologic findings from a group of patients who present retinitis pigmentosa affecting just one eye and use this information to propose mechanisms of disease pathogenesis. Methods This prospective cross-sectional study examined 5 patients, all female, from 8 to 60 years old. The study was conducted in 4 university hospitals. The patients were selected according to the characteristics of ocular involvement, notably unilateral presentation of similar anatomic and functional abnormalities. Full-field electroretinogram, fundus photography, fundus autofluorescence, infrared imaging, optical coherence tomography, and genetic testing were performed. Results Full-field electroretinogram showed unilateral decrease in amplitude and increase in implicit time; autofluorescence showed unilateral areas of decreased intensity. The USH2AW4149R mutation was confirmed in one patient. Conclusions Imaging and functional testing are important in elucidating the unilateral pattern of the disease and in monitoring these individuals. Mosaicism or somatic mutation may cause unilateral genetic disease presentation.

Engineering erythrocytes for the modulation of drugs' and contrasting agents' pharmacokinetics and biodistribution

Pharmacokinetics, biodistribution, and biological activity are key parameters that determine the success or failure of therapeutics. Many developments intended to improve their in vivo performance, aim at modulating concentration, biodistribution, and targeting to tissues, cells or subcellular compartments. Erythrocyte-based drug delivery systems are especially efficient in maintaining active drugs in circulation, in releasing them for several weeks or in targeting drugs to selected cells. Erythrocytes can also be easily processed to entrap the desired pharmaceutical ingredients before re-infusion into the same or matched donors. These carriers are totally biocompatible, have a large capacity and could accommodate traditional chemical entities (glucocorticoids, immunossuppresants, etc.), biologics (proteins) and/or contrasting agents (dyes, nanoparticles). Carrier erythrocytes have been evaluated in thousands of infusions in humans proving treatment safety and efficacy, hence gaining interest in the management of complex pathologies (particularly in chronic treatments and when side-effects become serious issues) and in new diagnostic approaches.

Pseudo-Vitelliform Macular Detachment and Cuticular Drusen: Exclusion of 6 Candidate Genes

Purpose: The etiology and genetic cause of pseudo-vitelliform macular detachment with cuticular drusen (PVMD/CD) are unknown; nor is it clear if this phenotype represents a separate disease entity, or is a sub-phenotype of disorders with overlapping clinical presentation. To answer this question, we screened a cohort of patients affected with PVMD/CD for variation in six plausible candidate genes (ABCA4, VMD2, TIMP-3, peripherin/RDS, fibulin 5 (FIBL5) and complement factor H (CFH)) associated with diseases of overlapping phenotypes. Methods: Twenty-eight patients, diagnosed with pseudo-vitelliform macular detachment and cuticular drusen, were evaluated by clinical examination, fundus photography, fluorescein angiography and autofluorescence imaging. DNA from all study subjects were screened for variants in the ABCA4, VMD2, TIMP-3, peripherin/RDS, FIBL5 and CFH genes by a combination of DHPLC, array screening and direct sequencing. Results: All patients presented with cuticular drusen; pseudo-vitelliform detachment was seen in 21 cases, while atrophic changes following regression of the detachment were seen in the remaining 7 subjects. Visual acuity ranged from 20/20 to CF. The screening revealed an I32V mutation in peripherin/RDS in one patient and 2ABCA4 variants, T897I and G1961E, in 2 more patients. No amino acid-altering variants were detected in VMD2, TIMP-3, and FIBL5 genes. The frequency of the CFH Y402H variant in this cohort corresponded to that detected in the general population. Conclusions: Screening of 6 candidate genes detected possibly disease-associated mutations in only 3/28 (10.7%) of patients presenting with PVMD/CD, eliminating these genes as causal for this phenotype.

INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR MACULAR HOLE SURGERY WITHOUT EXTRA MANIPULATION OF THE FLAP

Purpose: To determine whether surgical manipulation steps of the internal limiting membrane (ILM) flap, such as ILM trimmed, ILM tuck inside the hole, ILM massage, are mandatory to obtain satisfactory outcomes for the repair of large stage IV idiopathic macular hole using the inverted ILM flap technique. Methods: In this interventional comparative prospective single-masked study, 81 eyes were randomized into 2 treatments groups. In Group 1 (41 eyes), the classic inverted ILM flap technique was performed. In Group 2 (40 eyes), a modified procedure was used: after ILM peeling, no extra flap manipulation was performed. The macular hole was covered by the inverted ILM flap because of the air pressure at the time of the fluid–air exchange. Results: At 12 months, macular hole closure was observed in 40 eyes (97.6%) in Group 1 and in 39 eyes in Group 2 (97.5%). U-shape closure rate, ellipsoid zone defects, and external limiting membrane defects were similar in both groups. The results indicate no statistical difference in anatomical and functional success between both groups. Conclusion: The macular hole closure rate, improved visual acuity, and no extra complications indicate noninferiority of the modified inverted ILM technique. Internal limiting membrane finishing, tucking, and massage may not be required to obtain surgical success.

Amniotic membrane transplantation in the surgical management of symblepharon following toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a rare, potentially life-threatening acute condition, whose pathophysiology is not completely understood, but there is a certain agreement that it consists of a cell-mediated cytotoxic reaction against keratinocytes, altered by drugs or their metabolites. 1–3 Early recognition and withdrawal of the suspected drug are the main recommended procedures. 3 Therapeutic goals in the acute phase are directed toward promotion of wound healing, prevention of sepsis and management of multisystem failure. 4 In those patients who survive, ocular complications represent the most significant long-term sequelae and occurs in about 50% of cases. 5