Strabismus in Bronzino's paintings: a hallmark of a realistic painter?

The present article analyses eleven paintings of Bronzino, one of the major painters of the late Italian Mannerism, in which the sitters are portrayed with deviating eyes. The reasons why Bronzino may have included a truant eye in his subjects are herein discussed. We consider the 'wandering' eye as a hallmark of Bronzino's style. The inclusion of strabismus may be part of the Mannerism tendency of using exaggerated hallmarks but pursuing at the same time an increasing realism that was typical of the 15th and 16th century movements.

RESIDUAL INTRARETINAL EDEMA AFTER 25-GAUGE VITRECTOMY AND MACULAR PUCKER REMOVAL: Is Intraoperative Sustained-release Dexamethasone a Real Treatment Option?

PURPOSE: To investigate the efficacy and safety of intraoperative slow-release dexamethasone implant and 25-gauge (G) vitrectomy plus epiretinal membrane removal in patients affected by idiopathic macular pucker. METHODS: In this randomized, clinical, multicenter study, 60 eyes of 60 pseudophakic eyes having idiopathic macular pucker were enrolled. Thirty eyes underwent 25-G pars plana vitrectomy and internal limiting membrane peeling ("Control group"), whereas 30 eyes underwent 25-G pars plana vitrectomy and internal limiting membrane peeling combined with dexamethasone implant ("DEX group"). Best-corrected visual acuity was investigated using Snellen visual acuity ratio. Anatomical outcomes (foveal thickness and total macular volume) were analyzed with spectral domain optical coherence tomography. RESULTS: After 6-month follow-up, best-corrected visual acuity significantly increased in each group (P < 0.05), but there were no significant differences between groups (P = 0.60). Foveal thickness showed a significant decrease in both groups (P < 0.05), but no differences were seen between groups (P = 0.80). Finally, also total macular volume decreased significantly in both groups at the last follow-up visit (P < 0.05), but both groups a showed similar trend (P = 0.12). CONCLUSIONS: Intraoperative sustained-release dexamethasone implant, a powerful antiinflammatory agent with significant efficacy in vitrectomized eyes, did not result in a significant change in macular thickness and volume compared with the vitrectomy alone without dexamethasone implant at 6-month follow-up. These data support the hypothesis that its etiology does not seem to be mainly related to an inflammatory process.

Analysis of Choroidal Thickness Change after 25-Gauge Vitrectomy for Idiopathic Epiretinal Membrane with or without Phacoemulsification and Intraocular Lens Implantation.

PURPOSE: This study aimed to evaluate choroidal thickness modifications before and after vitrectomy with or without phacoemulsification for idiopathic epiretinal membrane in the operated eye and in the unaffected fellow eye. METHODS: In total, 53 eyes of 53 patients underwent 25-gauge pars plana vitrectomy plus internal limiting membrane peeling and air tamponade. Twenty-seven eyes underwent combined surgery with phacoemulsification and intraocular lens implantation. Choroidal thickness was measured using enhanced deep image spectral-domain optical coherence tomography at the fovea and at 500 and 2,500 µm from the fovea. Fellow eyes without any previous ocular surgery history served as controls. RESULTS: Baseline comparison did not show significant differences between study and fellow eyes (p > 0.05). Choroidal thickness significantly decreased in the subfoveal area (p = 0.004) as well as at 500 µm (p = 0.026) and 2,500 µm nasally (p = 0.019) and at 500 µm (p = 0.039) and 2,500 µm (p = 0.005) temporally to the fovea. No significant changes were observed postoperatively in the superior and inferior areas (p > 0.05). No differences were found between eyes which underwent combined surgery and those which underwent vitrectomy alone (p > 0.05). The unaffected eyes did not show any significant changes (p > 0.05). CONCLUSIONS: Comparison of baseline values did not show any differences between affected and unaffected eyes, meaning that choroidal thickness was not influenced by the development of epiretinal membrane. Vitrectomy plus epiretinal and inner limiting membrane removal may influence choroidal homeostasis, leading to a decrease in choroidal thickness in the subfoveal, nasal, and temporal areas. Combined surgery did not show significant differences when compared to vitrectomy alone.

ADJUSTABLE MACULAR BUCKLING FOR FULL-THICKNESS MACULAR HOLE WITH FOVEOSCHISIS IN HIGHLY MYOPIC EYES: Long-Term Anatomical and Functional Results.

PURPOSE: To assess functional and structural outcome after adjustable macular buckling for the treatment of foveoschisis (FS), associated with full-thickness macular hole (FTMH) in highly myopic eyes. METHODS: Eighteen consecutive patients who underwent adjustable macular buckling for FS associated with FTMH were included in this prospective study. Three cases were not included in the analysis due to short follow-up period (less than 3 months). Outcome measures included anatomical success rate with FS resolution and FTMH closure, best-corrected visual acuity, mean retinal sensitivity, central retinal thickness, and fixation site and stability. RESULTS: Foveoschisis resolution and FTMH closure were observed in all cases between 1 month to 3 months after surgery. At 24 months of follow-up visit visual acuity improved in 13/15 eyes (86.7%) and remained stable in 2 (13.3%). Mean retinal sensitivity showed significant improvement from baseline 5.69 ± 3.52 dB to final 8.35 ± 3.86 dB; P < 0.001. Fixation stability inside central 4° improved from baseline 58.5 ± 17.8% to final 73.7 ± 23.0%; P = 0.009. Central retinal thickness did not change significantly throughout follow-up. No FTMH or FS recurrence occurred and no surgical complications arose. CONCLUSION: Adjustable macular buckling exoplant may represent an effective surgical option for the treatment of FS associated with FTMH in highly myopic eyes. Adjustable macular buckling showed high closure rate and virtually no tendency to recur. Functional results and safety are also interesting because vision improved and retinal thickness did not reduce significantly at 24 months of follow-up.

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.

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.

PURPOSE: The 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. METHODS: We 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. FINDINGS: We 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. IMPLICATIONS: Analysis 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.

Intravitreal ranibizumab for predominantly hemorrhagic choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the effects of intravitreal ranibizumab monotherapy on predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. MATERIALS AND METHODS: Twenty-two consecutive eyes with hemorrhagic neovascularization were treated with 3 monthly intravitreal ranibizumab injections. Additional injections were administered according to retreatment criteria during 12 months of follow-up. RESULTS: A mean of 6.64 ± 1.36 injections was administered. Overall, the mean visual acuity increased from 10.90 ± 6.02 to 12.81 ± 8.34 ETDRS letters (p > 0.05) at 12 months. The 'early treatment group' gained a mean of 2.83 ± 2.24 ETDRS letters (p < 0.05), while the 'late treatment group' gained a mean of 0.30 ± 1.25 ETDRS letters (p > 0.05) with significant differences between the groups (p < 0.05). A progressive resolution of macular bleeding was registered in 20 patients (mean time: 5.3 ± 1.6 months). CONCLUSIONS: Ranibizumab injections can be considered a beneficial approach for the management of predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. Furthermore, the time interval between hemorrhage and the first injection seems to be an important predicting factor of final visual acuity.

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.

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.

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.

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 Bruch's 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.

The contribution of Aulus Cornelius Celsus (25 B.C.-50 A.D.) to eyelid surgery.

An accurate study of ancient medicine reveals that our forebears developed a large number of surgical ideas and techniques considered to be quite modern. Although the contribution of Aulus Cornelius Celsus to the development of several branches of surgery has already been celebrated, scant attention has been focused on his description of eyelid surgery in the seventh book of his encyclopedia, De Medicina octo libri. Although the practice was quite advanced by that time, the first century A.D., Celsus was the first among the Greco-Roman authors to deal systematically with ophthalmology and oculoplastic surgery. He was a compiler, and many of his "innovations" were in fact done in principle by others. Yet it is almost certain that the surgical procedures presented were introduced more than 15 centuries before the time of Celsus by Egyptians, Indian surgeons, and Greek and Alexandrian doctors. The burning of the Ancient Library of Alexandria as well as the perishing of many writings of pioneer physicians resulted in a tragic loss of ancient knowledge for posterity. Celsus, whose work has been preserved in our time, helped to publicize this ancient knowledge, and perhaps because of the loss of so much early medical literature, became one of the most influential experts on ancient medicine. An analysis of how previous authors have influenced Celsus' description of eyelid surgery and reflections on how modern his ideas (or those of his time) were are presented in the paper.

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.

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.