Stefano Lazzeri

Blindness following cosmetic injections of the face.

Background: Complications following facial cosmetic injections have recently heightened awareness of the possibility of iatrogenic blindness. The authors conducted a systematic review of the available literature to provide the best evidence for the prevention and treatment of this serious eye injury. Methods: The authors included in the study only the cases in which blindness was a direct consequence of a cosmetic injection procedure of the face. Results: Twenty-nine articles describing 32 patients were identified. In 15 patients, blindness occurred after injections of adipose tissue; in the other 17, it followed injections of various materials, including corticosteroids, paraffin, silicone oil, bovine collagen, polymethylmethacrylate, hyaluronic acid, and calcium hydroxyapatite. Conclusions: Some precautions may minimize the risk of embolization of filler into the ophthalmic artery following facial cosmetic injections. Intravascular placement of the needle or cannula should be demonstrated by aspiration before injection and should be further prevented by application of local vasoconstrictor. Needles, syringes, and cannulas of small size should be preferred to larger ones and be replaced with blunt flexible needles and microcannulas when possible. Low-pressure injections with the release of the least amount of substance possible should be considered safer than bolus injections. The total volume of filler injected during the entire treatment session should be limited, and injections into pretraumatized tissues should be avoided. Actually, no safe, feasible, and reliable treatment exists for iatrogenic retinal embolism. Nonetheless, therapy should theoretically be directed to lowering intraocular pressure to dislodge the embolus into more peripheral vessels of the retinal circulation, increasing retinal perfusion and oxygen delivery to hypoxic tissues. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

Macular pucker: To peel or not to peel the internal limiting membrane? a microperimetric response

Background: To compare functional and anatomical outcomes after idiopathic macular pucker removal between eyes that underwent internal limiting membrane (ILM) peeling and eyes that did not. Methods: In this multicentric, randomized clinical trial, 60 eyes of 60 patients affected with idiopathic macular pucker were enrolled. Thirty eyes underwent 23-gauge pars plana vitrectomy associated with ILM peeling (“ILM peeling group”), whereas 30 eyes did not undergo ILM peeling (“ILM not peeling group”). Retinal sensitivity, frequency of microscotomas, and all the other microperimetric parameters were tested by MP1 microperimetry. Best-corrected visual acuity was investigated with the Early Treatment Diabetic Retinopathy Study chart. Anatomical outcomes were analyzed with spectral domain optical coherence tomography. Results: After a 12-month follow-up, the mean retinal sensitivity in the 4° central area showed a greater and faster recovery in the ILM not peeling group than in the ILM peeling group (P = 0.041). The number of absolute microscotomas (0 dB) within the 12° central retinal area was significantly higher in the ILM peeling group than in the ILM not peeling group (P = 0.044). Conclusion: The ILM not peeling group seems to show better outcomes than the ILM peeling group as measured by mean retinal sensitivity and number of microscotomas after a 12-month follow-up.

In vivo analysis of conjunctiva in gold micro shunt implantation for glaucoma

Aims To describe the conjunctival epithelial features seen with in vivo confocal microscopy (IVCM) after gold micro shunt (GMS) implantation in the suprachoroidal space, in patients with uncontrolled glaucoma. Methods This was an observational case series study. Fourteen eyes of 14 consecutive glaucomatous patients with a history of multiple failed incisional surgeries followed by GMS implantation were evaluated with a digital confocal laser-scanning microscope (HRT II Rostock Cornea Module). Patients were divided into two groups: successful implantations (Group 1: eight patients, eight eyes), defined as a one-third reduction in preoperative intraocular pressure (IOP) with or without antiglaucoma medications and failed implantations (Group 2: six patients, six eyes) as a less than one-third reduction in preoperative IOP with maximal tolerated medical therapy. The examination was performed from 3 to 20 months (mean 15.4±5.4) postoperatively. Conjunctival mean microcyst density (MMD: cysts/mm2) and mean microcyst area (MMA: μm2) were the main outcome measurements. Results The mean postoperative IOP was statistically different between the two groups (p<0.05), with the values of 14.3±2.77 and 32.3±8.01 mm Hg in Groups 1 and 2, respectively. When comparing successful with failed implantation, the IVCM analysis showed a greater MMD (p<0.01) and MMA (p<0.01). Clinical evidence of filtering bleb was not found in any of the patients. Conclusions Successful GMS implantation significantly increased conjunctival microcysts density and surface at the site of the device insertion. These findings suggest that the enhancement of the aqueous filtration across the sclera may be one of the possible outflow pathways exploited by the shunt.

Supraciliary shunt in refractory glaucoma

Aims This study aimed to evaluate the efficacy of Gold Micro Shunt (GMS) for suprachoroidal drainage in patients with refractory glaucoma. Methods This is a prospective uncontrolled case series study. Fifty-five eyes of 55 patients were included. Study eyes underwent GMS implantation in the supraciliary space. Follow-up visits were performed on day 1, week 1 and months 1, 3, 6, 12 and 24; patients underwent slit-lamp examination, Goldmann applanation tonometry, ultrasound biomicroscopy and gonioscopy. Results Before inclusion, the eyes underwent an average (±SD) of 1.9±0.7 (range 1–5) previous glaucoma surgery procedures. Forty eyes were pseudophakic, 12 were phakic and 3 were aphakic. The mean baseline intraocular pressure was 30.8±8.8 mm Hg (range 22–58 mm Hg) despite maximal medical treatment. After 2 years of follow-up, qualified success was achieved in 37 eyes (67.3%) and complete success was achieved in 3 eyes (5.5%). In success group patients, mean intraocular pressure decreased from 27.6±6.9 at baseline to 13.7±2.98 mm Hg after 2 years of follow-up; the mean (±SD) number of medications was 1.4±0.7 in the postoperative phase, compared with a value of 2.5±0.9 in the preoperative phase. Mild side effects occurred in 21 patients, with mild or moderate postoperative hyphema being the most frequent one. Development of a thin membrane, obstructing the anterior holes, was the most important factor affecting the efficacy of this device; it was found to be present in 12 patients from the failure group (66.7% of failures). Conclusion GMS achieved qualified success in about 67.3% of eyes with uncontrolled refractory glaucoma with a low rate of complications.

Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration

Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruchs membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.

VEGF-A polymorphisms predict short-term functional response to intravitreal ranibizumab in exudative age-related macular degeneration

AIM To investigate the association between VEGF gene SNPs and early response to intravitreal ranibizumab for exudative age-related macular degeneration. MATERIALS & METHODS Sixty-four patients (64 eyes) were prospectively enrolled and treated for neovascular age-related macular degeneration with ranibizumab monotherapy. Visual acuity was measured using the ETDRS chart. A loading phase of 3 monthly intravitreal injections of ranibizumab 0.5 mg/0.05 ml was performed. The analyzed VEGF-A gene SNPs were rs699947 (-2578A/C) and rs1570360 (-1154G/A); the allelic discrimination was performed in real-time PCR platform. The difference of best corrected visual acuity (ETDRS letters) read before and after treatment was considered as functional outcome. RESULTS Ranibizumab was significantly more effective as measured by best corrected visual acuity in patients harboring the VEGF-A -2578C allele (from +6.26 to +7.44 ETDRS letters), whereas patients carrying the VEGF-A -2578AA genotype revealed an absence of early functional response to ranibizumab (-1.78 ETDRS letters; p = 0.0192). CONCLUSION This study suggests that the VEGF-A -2578A/C SNP may represent an important molecular determinant of the early functional outcome of ranibizumab. Original submitted 3 December 2012; Revision submitted 18 February 2013.

Aflibercept administration in neovascular age-related macular degeneration refractory to previous anti-vascular endothelial growth factor drugs: a critical review and new possible approaches to move forward

PurposeThe recent introduction of anti-VEGF drugs has widely changed the prognosis of exudative age-related macular degeneration (AMD), even if a variable percentage of patients showed an insufficient response. Aflibercept is a new anti-VEGF drug approved by FDA for the treatment of exudative AMD with a wider binding capacity than either bevacizumab or ranibizumab. Therefore, the purposes were as follows: (i) to report anatomical and functional outcomes of switching from bevacizumab/ranibizumab to aflibercept previously described in the scientific literature, (ii) to hypothesize the possible pathophysiological mechanisms of the resistance and tachyphylaxis to anti-VEGF drugs, and (iii) to suggest possible clinical actions to increase the chances of success for such difficult cases.MethodsWe reviewed the available scientific literature in Medline, Cochrane database, Current Contents, PubMed, and cross-referencing from identified articles, regarding the treatment of exudative AMD patients refractory to bevacizumab and/or ranibizumab and switched to aflibercept monotherapy. We included in this review all the cases in which the diagnosis of refractory or resistant exudative AMD was properly made, and the results of at least one aflibercept injection were described.FindingsWe reported the outcomes of 21 papers for a total of 1066 eyes affected by exudative AMD resistant to previous anti-VEGF drug injections and switched to aflibercept. Enrolled reports were divided into two groups: 5 prospective reports and 16 retrospective reports. All the reported papers conclude their analysis, stating that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients.ImplicationsAnalysis of the papers reported in this review demonstrates that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. The mechanism for these effects is not yet completely understood.

The rs2071559 AA VEGFR-2 Genotype Frequency Is Significantly Lower in Neovascular Age-Related Macular Degeneration Patients

In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD) cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377) of VEGF-A receptor-2 (VEGFR-2) gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33%) in patients with AMD than in the control subjects (34.62%; P = 0.0095, chi-square test; P corr = 0.038; OR = 0.42, 95% CI 0.22 to 0.82). In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

IL-8 and VEGFR-2 polymorphisms modulate long-term functional response to intravitreal ranibizumab in exudative age-related macular degeneration.

AIM To investigate possible associations between VEGFR-2 and IL-8 gene SNPs and 1-year response to intravitreal ranibizumab for exudative age-related macular degeneration. MATERIALS & METHODS Sixty-four eyes underwent a loading phase of three monthly intravitreal injections of ranibizumab 0.5 mg/0.05 ml followed by Pro Re Nata retreatment. VEGFR-2 rs2071559 (-604 A/G) and IL-8 rs4073 (-251 A/T) were analyzed. RESULTS Ranibizumab was significantly more effective as measured by visual acuity in patients harboring the IL-8 rs4073 TT genotype (p = 0.045), whereas patients carrying the VEGFR-2 rs2071559 CC genotype revealed better functional response as measured by mean retinal sensitivity (p = 0.034). CONCLUSION IL-8 rs4073 and VEGFR-2 rs2071559 genotypes may represent important molecular determinants to modulate final outcomes in neovascular age-related macular degeneration patients.

Bimatoprost 0.01% vs bimatoprost 0.03%: a 12-month prospective trial of clinical and in vivo confocal microscopy in glaucoma patients

PurposeTo evaluate the safety of two commercially available formulations of bimatoprost eye drops: 0.03 and 0.01% ophthalmic solutions.MethodsThis was a randomized, prospective, parallel-group, open-label, cohort study. A total of 60 glaucoma patients (60 eyes) under bimatoprost 0.03% monotherapy since at least 1 year were enrolled. Selected patients were randomized to receive a single drop of bimatoprost 0.01% (n=30) or bimatoprost 0.03% (n=30) ophthalmic solutions for 12 months. Statistical analysis was performed using paired t-test and repeated measures ANOVA test.ResultsGlobal clinical score (the sum of pruritus, stinging/burning, blurred vision, sticky eye sensation, eye dryness sensation, and foreign body sensation) significantly decreased in the bimatoprost 0.01% group from baseline 4.7±3.8 to 2.9±2.3 (P<0.001) and 2.5±2.0 (P<0.001) at 6-month and 12-month follow-ups, respectively. Comparison between groups showed differences at both follow-up visits (P=0.003 and P<0.001, respectively). In vivo confocal microscopy revealed a significant increase in goblet cell density in the bimatoprost 0.01% group compared with the bimatoprost 0.03% group (P<0.001 at both follow-up visits). All functional parameters and conjunctival hyperemia improved in the bimatoprost 0.01% group at each follow-up visit (P<0.05) and in comparison with bimatoprost 0.03% (P<0.05).ConclusionThe results of this trial suggest that bimatoprost 0.01% eye drops seem to decrease the ocular discomfort with respect to bimatoprost 0.03% eye drops.