Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease.

Objective: To investigate preclinical data regarding the efficacy and biocompatibility of a bispecific protein, RO-101, with effects on VEGF-A and angiopoietin-2 (Ang-2) for use in retinal diseases. Design: Experimental study. Subjects: Brown Norway rats and New Zealand White Cross rabbits. Methods: Preclinical study data of RO-101 in terms of target-specific enzyme-linked immunosorbent assay binding affinity to VEGF-A and Ang-2, vitreous half-life, inhibition of target-receptor interaction, laser choroidal neovascular membrane animal model, human umbilical vein endothelial cell migration, and biocompatibility was obtained. Where applicable, study data were compared with other anti-VEGF agents. Main Outcome Measures: Binding affinity, half-life, biocompatibility, and efficacy of RO-101. Neovascularization prevention by RO-101. Results: RO-101 demonstrated a strong binding affinity for VEGF-A and Ang-2 and in vitro was able to inhibit binding to the receptor with higher affinity than faricimab. The half-life of RO-101 is comparable to or longer than current VEGF inhibitors used in retinal disease. RO-101 was found to be biocompatible with retinal tissue in Brown Norway rats. RO-101 was as effective or more effective than current anti-VEGF therapeutics in causing regression of neovascular growth in vivo. Conclusions: RO-101 is a promising candidate for use in retinal diseases. In preclinical models, RO-101 demonstrated similar or higher regression of neovascular growth to current anti-VEGF therapeutics with comparable or longer half-life. It also demonstrates a strong binding affinity for VEGF-A and Ang-2. It also was shown to be biocompatible with retinal tissue in animal studies, indicating potential compatibility for use in humans. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

ALTERNATIVE INTRAVITREAL ANTIBIOTICS: A Systematic Review for Consideration in Recalcitrant or Resistant Endophthalmitis.

PURPOSE: To organize, categorize, and create a quick reference guide for the use of intravitreal antibiotic alternatives to the standard combination of vancomycin and ceftazidime for the treatment of endophthalmitis. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The authors searched for all available information regarding intravitreal antibiotics in the last 21 years. Manuscripts were selected according to relevance, level of information, and the available data regarding intravitreal dose, potential adverse effects, bacterial coverage, and relevant pharmacokinetic information. RESULTS: The authors included 164 of 1810 manuscripts. The antibiotics were classified according to their class into fluoroquinolones, cephalosporins, glycopeptide and lipopeptide, penicillins and beta-lactams, tetracyclines, and miscellaneous. The authors also included information regarding intravitreal adjuvants for the treatment of endophthalmitis and one ocular antiseptic. CONCLUSION: The treatment of infectious endophthalmitis is a therapeutic challenge. The current review summarizes the properties of possible intravitreal antibiotic alternatives that should be considered in cases of suboptimal response to initial treatment.

Combined Therapeutic Penetrating Keratoplasty and Pars Plana Vitrectomy for the Treatment of Infectious Keratitis Endophthalmitis: Mexican Endophthalmitis Study Group Protocol 4.

PURPOSE: The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis. METHODS: This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up. RESULTS: The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%). CONCLUSIONS: Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.

Ultrasound-Guided Pars Plana Vitrectomy.

PURPOSE: To assess the feasibility of a novel surgical technique that combines B-scan ultrasound with modern vitrectomy techniques. METHODS: Patients with a clinical diagnosis of infectious keratitis endophthalmitis, which were scheduled for pars plana vitrectomy and ruled out as candidates for transient keratoprosthesis, were enrolled. The ultrasound probe was placed over the eye to use the images to witness the vitreous movement around the cutter and to establish its position in relation to the retinal wall. The procedure was performed in at least four ultrasound projections (longitudinal-9,6, 3, and 12). All patients were followed for three months, and in each visit, the visual acuity and the presence of adverse effects were assessed. RESULTS: Overall, 12 patients (mean age: 56.2 ± 18.4 years) were enrolled. Visual acuity at baseline was 2.3 ± 0.25 logarithm of the minimum angle of resolution. Sixty-six percent achieved inactivation of endophthalmitis. Two patients had evisceration caused by uncontrolled infection, and two more had retinal detachment during follow-up. Visual acuity at the end of follow-up was 2.1 ± 0.3 logarithm of the minimum angle of resolution ( P = 0.5). CONCLUSION: Ultrasound-guided vitrectomy is a feasible surgical technique. More studies are needed to assess its safety profile and optimize outcomes.

Kocuria Endophthalmitis: Clinical Spectrum and Long-term Outcomes.

PURPOSE: To expand the knowledge regarding the clinical presentation of Kocuria endophthalmitis. METHODS: We included six cases of Kocuria endophthalmitis between January 2018 and December 2020. From all cases, we collected general demographic data, relevant medical, ophthalmological history, microbiological and antibiotic sensitivity results. All cases had a minimum follow-up of 9 months. All cases were treated with intravitreal moxifloxacin and dexamethasone and pars plana vitrectomy. Undiluted vitreous, corneal, conjunctival, and aqueous samples were cultured and analyzed with the Vitek 2 system. RESULTS: The prevalence of Kocuria endophthalmitis was 6%. (95%CI: 2.26%-12.73%). The mean age at diagnosis was 60.5 ± 15.5 years. All patients had poor visual acuity, severe pain, and severe conjunctival hyperemia at diagnosis. Only one case had a significant improvement in visual acuity at the end of the follow-up. CONCLUSION: Kocuria spp are an emerging cause of endophthalmitis and should be considered as part of the differential diagnosis.

Risk of Posterior Capsular Rupture during Phacoemulsification in Patients with the History of Anti-VEGF Intravitreal Injections: Results from the Pan-American Collaborative Retina Study (PACORES) Group.

PURPOSE: To assess the risk for capsular rupture during routine phacoemulsification in patients with a history of anti-VEGF injections and other possible risk modifiers such as treatment patterns, type of anti-VEGF agent, and experience of the surgeon, among others. METHODS: This study reviewed the medical records of 11,129 patients from 7 different hospitals in 5 countries. The study included 939 patients that underwent routine phacoemulsification and had a history of anti-VEGF therapy. We excluded patients with known risk factors for capsular rupture, as well as patients with a history of other retinal procedures. The study extracted data regarding general demographics, the number of previous injections, type of anti-VEGF agent, details of cataract surgery, and anti-VEGF treatment patterns. RESULTS: Overall prevalence of posterior capsular rupture: 7.45% (95% CI: 5.9-9.32%). The mean number of injections per patient was 3.37 ± 2.8. More than 50% of the patients received their last anti-VEGF injection within three months before cataract surgery. The complication rate during intravitreal injections was 1.07%. In the univariate analysis, the experience of the cataract surgeon (inexperience surgeons; OR: 2.93) and the history of prior anti-VEGF therapy (OR: 1.77) were significant risk indicators for PCR (p < 0.05). However, after controlling for age in the multivariate analysis, the trend did not reach a statistical significance. CONCLUSION: The risk for capsular rupture is higher in patients with a history of intravitreal anti-VEGF injections.

Autologous full-thickness retinal transplant for refractory large macular holes.

BACKGROUND: Despite the constant refinement of techniques and surgical aids, extremely large and refractory macular holes continue to have poor surgical outcomes with the current standard of care. The objective of the present study is to assess the anatomical and functional outcomes, as well as the structural change through time, of the optical coherence tomography of patients with refractory macular holes treated with a full-thickness autologous retinal transplant. METHODS: Prospective, case series. We include patients with a clinical diagnosis of refractory macular holes with a minimum diameter of at least 500 µm. All the patients had a comprehensive ophthalmological examination, which included a best-corrected visual acuity assessment, fundus examination, and optical coherence analysis. All the patients underwent a 23-gauge pars plana vitrectomy with a full-thickness retinal transplant and silicone oil tamponade (5000 cs<). Follow-up was done at 1, 3, 6, and 12 months. Statistical analysis was done with a test for repeated measurements and Bonferroni correction, with an alpha value of 0.05 for statistical significance and a Mann-Whitney U test for nonparametric continuous variables. RESULTS: We enrolled 13 eyes from 13 patients (mean age: 67.15 years) with refractory macular holes, with a mean base diameter of 1615.38 ± 689.19 µm and a minimum diameter of 964.08 ± 709.77 µm. The closure rate after 12 months of follow-up was 76.92%. Six patients with a closed macular hole at the end of the follow-up had complete recovery of the myoid/ellipsoid layer. The remaining showed a 44.9% reduction of the initial gap. Most patients formed a pseudofovea and normalization of the internal retinal layers. Despite a positive trend toward visual recovery (p = 0.034), after the correction of the alpha value, the change lost its statistical significance. During follow-up, one patient developed mild proliferative vitreoretinopathy and epiretinal membrane without anatomical or functional consequences. CONCLUSIONS: An autologous full-thickness retinal transplant may improve the anatomical and structural outcome of patients with refractory macular holes. The full safety profile of this new technique is still unknown. More studies are needed in order to assess functional changes through time.

Bioceramic implant reduces intraocular VEGF levels.

Elevated intraocular levels of angiogenic cytokines such as vascular endothelial growth factor (VEGF) have been implicated the development of diabetic retinopathy. Over a decade of clinical evidence shows intravitreal injection of anti-VEGF agents is associated with decreased disease progression and preservation of vision. However, the treatment burden associated with monthly injections limits the effectiveness of existing anti-VEGF therapies. Current research has focused on sustained treatment paradigms such as longer acting drugs, drug delivery implants, and gene therapy. In this study, we tested a novel approach by dialyzing proteins from the vitreous using bioceramic implant composed of hydroxyapatite. Preliminary in vitro and in vivo studies demonstrate a high affinity and capacity for VEGF absorption. After three months implantation in New Zealand White Cross rabbits, the hydroxyapatite demonstrated good biocompatibility with no inflammation and normal retinal physiology and histology. These studies demonstrate that prolonged VEGF suppression intraocularly may be accomplished with a bioceramic implant.

Autofluorescence indexes as biomarkers for antiangiogenic loading dose outcome in diabetic macular edema.

PURPOSE: To evaluate the combination of fundus autofluorescence results with several clinical and structural variables into mathematical indexes to enhance their ability to predict visual and anatomical changes after the antivascular endothelial growth factor loading dose. METHODS: Patients with diabetic macular edema were enrolled. Each patient had a comprehensive ophthalmological examination, contrast sensitivity, optical coherence tomography, and fundus autofluorescence assessment. All patients received three monthly doses of ziv-aflibercept and were followed each month for response assessment. Autofluorescence was classified according to its level into five grades. The grades were combined with other variables (best-corrected visual acuity, contrast sensitivity, central macular thickness, macular cube volume, and macular cube average thickness) into normalized indexes. Statistical assessment was done using a Spearman's rank correlation coefficient, linear regression, and interobserver-agreement analysis. RESULTS: There was a strong correlation between the fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index at baseline with the best-corrected visual acuity after the third dose of ziv-aflibercept (rs = -0.78, p = .000 and rs = -0.68, p = .0009 respectively). The fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index, both at baseline had a mild correlation with the macular volume at 1 month of follow-up (rs = 0.56, p = .008 and (rs = 0.64, p = .002, respectively). CONCLUSION: This study suggests that it is possible to combine fundus autofluorescence results with functional and structural variables into normalized indexes that could potentially predict outcomes after antivascular endothelial growth factor loading dose in patients with diabetic macular edema.

Vitreous protein binding with nanopore dialysis membrane device.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the industrialized world, affecting over 8 million patients in the United State alone. While the wet (exudative) form of the disease is treated with intraocular injections, there are currently no approved therapies available for the dry (non-exudative) form of the disease which often affects both eyes in patients with AMD. Current research has focused on developing drugs that can be injected into the eye, but the treatment burden associated with monthly injections limits the effectiveness of this approach. Hence, there is a pressing need for a long-term therapeutic solution for patients suffering from this blinding disease. We detail a novel implantable intraocular device, which adsorbs and traps complement factors associated with AMD. In this study, we tested a novel approach by dialyzing proteins from the vitreous using biocompatible implants composed of a nanopore polyacrylonitrile polymer membrane. Preliminary in vitro and in vivo studies demonstrate a high affinity and capacity for complement protein absorption. After a three-month implantation in New Zealand White Cross rabbits, the implant demonstrated good biocompatibility with no inflammation and normal retinal physiology and histology. These studies demonstrate that prolonged CF suppression intraocularly may be accomplished with a nanopore polymer membrane.

A Proposed Method to Quantify Vitreous Hemorrhage by Ultrasound.

PURPOSE: To propose a method for quantification of vitreous hemorrhages (VH) termed minimum image gain (MIG). Therefore, to obtain MIG measurements in patients with VH and to compare them to normal controls; to compare results between graders; and to obtain and compare MIG from two different ultrasound systems. METHODS: Retrospective and cross-sectional, observational, and comparative study performed in two parts: Part 1) Retrospective comparison of MIG in VH vs controls by two experienced graders, with intra/inter-observer variability: MIG technique is described. MIG is performed retrospectively in two groups, VH patients and normal controls. Groups are compared with independent samples t-test. Intra- and interobserver variability between graders was obtained. Part 2) Cross-sectional analysis of variability from nonexperienced graders and with different ultrasound systems: MIG is performed in cross-sectional measurements of VH patients, by two unexperienced graders, and with two ultrasound systems. Interobserver variability and Bland-Altman plot with levels of agreement (LoA) were obtained. RESULTS: Part 1: 50 patients with VH resulted in mean MIG: 52.8 dB; 34 controls resulted in mean MIG: 77.97 dB. Independent samples t-test resulted in a statistical significant difference. Intra- and inter-observer variability resulted in an almost perfect agreement between experienced graders. Part 2: 63 patients with VH, mean MIG: 56.19 dB. Inter-observer variability resulted in a very high agreement between unexperienced observers. LoA resulted in a statistical difference between the two ultrasound systems. CONCLUSION: MIG may provide an objective and reproducible way to quantify vitreous hemorrhage density and potentially any vitreous humor opacity. Agreement is high even with unexperienced graders. However, the two ultrasound systems analyzed may not be interchangeable.

Assessment of Postural Compliance After Pneumatic Retinopexy.

PURPOSE: We describe the functioning of a novel device, aimed to assess patient head position after a pneumatic retinopexy. METHODS: We enrolled patients with the clinical diagnosis of rhegmatogenous retinal detachment. All patients were asked to wear a specially designed headband with a monitoring device composed of an accelerometer, gyroscope, and magnetometer, powered by a 3.7V lithium battery. Every 200 ms, the device measured neck flexion and extension, left and right rotation, and left and right flexion. Patients were asked to come back the next morning for follow-up and headband retrieving. RESULTS: The device was worn an average of 19.17 ± 2.1 hours and performed a mean number of 57,670 ± 8663 measurements without power failures or program errors. An acceptable head position was kept for a mean of 3.33 ± 1.8 hours. The hardest axis to maintain was the right and left flexion of the neck (5.5 ± 2.54 hours of acceptable positioning). CONCLUSION: Real-time monitoring of patient head position after a vitreoretinal procedure is feasible. Maintaining a fixed head position for more than 5 consecutive hours is difficult to achieve and physicians should consider this difficulty when planning treatment. TRANSLATIONAL RELEVANCE: In addition to a significant improvement to the basic design of similar devices, our device allows for assessment of patient adherence to postoperative instructions objectively for the first time to our knowledge. This information could be used in the future to elaborate more detailed position nomograms to improve outcomes.

Cilioretinal Artery Branch Avulsion Secondary to Surgical Embolectomy: Management and Outcome.

We report the trans-operative approach and short-term outcome of a patient who suffered a traumatic avulsion of the cilioretinal artery branch during the surgical management of a cilioretinal arterial branch occlusion (CRABO) with intraocular embolectomy. A patient with acute CRABO underwent a pars plana vitrectomy with in situ embolectomy. The blocked artery was incised using 25 gauge vertical scissors, and embolus manipulation was done using microsurgical forceps. During embolus extraction, the occluded cilioretinal artery and its branch were inadvertently avulsed and torn with subsequent intense bleeding. Laser and endodiathermy were used for acute hemostasis. The maneuvers created an unintended retinochoroidal anastomosis. Visual field improvement was noted 3 months after the surgery. In the event of a complicated surgical embolectomy with the avulsion of the artery, the formation of a retinochoroidal anastomosis and reperfusion of the occluded may occur along with the improvement of visual fields in some cases.

Anti-VEGF treatment switch in neovascular age-related macular degeneration: a comparison of aflibercept versus ranibizumab after a single-dose switch.

PURPOSE: To determine the effect achieved from a single dose of anti-VEGF treatment switch, in patients with nAMD previously treated with bevacizumab, switched to either aflibercept or ranibizumab, and to compare the response between aflibercept and ranibizumab. METHODS: In retrospective, observational, and comparative study, patients were divided into two groups: Group 1, patients switched to aflibercept; Group 2, patients switched to ranibizumab. Paired samples t test was performed to measure differences in central macular thickness (CMT). To compare whether there were differences between groups mixed-design ANOVA was used. RESULTS: In Group 1, CMT changed from 360.51 to 260.16 µm, presenting a significant mean difference from PreSwitch to PostSwitch of 100.34 µm (p = 0.002, paired samples t test). In Group 2, CMT changed from 366.33 to 260.72 µm, showing a significant difference from PreSwitch to PostSwitch of 105.61 µm (p ≤ 0.000, paired samples t test). The mixed-design ANOVA compared both groups and resulted in a nonsignificant value of 0.90. CONCLUSION: The effect achieved from a single dose in patients switched to aflibercept or ranibizumab reduced significantly CMT measurements. Comparing aflibercept and ranibizumab, the effect appears to be similar in both drugs, in terms of reduction of CMT.

Secondary hyperhomocysteinemia-related occlusive retinal vasculopathy: A case report.

PURPOSE: To report a case of occlusive retinal vasculopathy, secondary to hyperhomocysteinemia. OBSERVATIONS: A 43-year-old male was examined at the retina outpatient clinic due to complaints of bilateral decrease in visual acuity. The patient underwent a comprehensive ophthalmological examination, wide-field fundus photographs and fluorescein angiography, as well as spectral domain optical coherence tomography with enhanced-deep imaging. The patient had a significant medical history of chronic kidney disease and progressive bilateral vision loss over the last two years, which worsened in the left eye during the past 3 months. Fundus examination revealed a vitreous hemorrhage in the left eye and bilateral proliferative retinopathy. Blood glucose and systemic blood pressure were unremarkable. Plasma homocysteine was reported at >500 µmol/L, which is higher than the corrected reference range by age. CONCLUSION AND IMPORTANCE: Hyperhomocysteinemia is a rare but well-known disease, capable of accelerating atherosclerotic disease and generating a prothrombotic state that can lead to multiple systemic complications. Despite its low incidence, the disease should be part of the differential diagnosis in patients with bilateral proliferative retinopathy, in the absence of diabetes mellitus and systemic hypertension.

Cilioretinal artery branch avulsion secondary to surgical embolectomy: management and outcome. Case report / Avulsão do ramo da artéria ciliorretiniana secundária à embolectomia cirúrgica: manejo e desfecho. Relato de caso

ABSTRACT We report the trans-operative approach and short-term outcome for a patient who suffered a traumatic avulsion of the cilioretinal artery branch during the surgical management of a cilioretinal arterial branch occlusion with intraocular embolectomy. The patient underwent a pars plana vitrectomy with in situ embolectomy. The blocked artery was incised using 25 Ga vertical scissors, and embolus manipulation was performed using microsurgical forceps. During embolus extraction, the occluded cilioretinal artery and its branch were inadvertently avulsed and torn with subsequent intense bleeding. Laser and endodiathermy were used for acute hemostasis. The maneuvers created an unintended retinochoroidal anastomosis. Visual-field improvement was noted three months after the surgery. In the event of a complicated surgical embolectomy with the avulsion of the artery, the formation of a retinochoroidal anastomosis and reperfusion of the occluded artery may occur along with the improvement of the visual field in some cases.

RESUMO Relatamos a abordagem transoperatória e o desfecho em curto prazo de um paciente que sofreu uma avulsão traumática do ramo da artéria ciliorretiniana durante o tratamento cirúrgico de uma oclusão do ramo arterial ciliorretiniano com embolectomia intraocular. O paciente foi submetido a uma vitrectomia pars plana com embolectomia in situ. A artéria bloqueada foi incisada com uma tesoura vertical de 25 Ga e a manipulação do êmbolo foi feita com pinça microcirúrgica. Durante a extração do êmbolo, a artéria ciliorretiniana ocluída e seu ramo foram inadvertidamente avulsionados e rasgados com sangramento intenso subsequente. Laser e endodiatermia foram utilizados para hemostasia aguda. As manobras criaram uma anastomose retinocoroidiana não intencional. Melhora do campo visual foi observada três meses após a cirurgia. No caso de uma embolectomia cirúrgica complicada com a avulsão da artéria, a formação de uma anastomose retinocoroidiana e reperfusão da artéria ocluída pode ocorrer juntamente com a melhora do campo visual em alguns casos.

Cilioretinal artery branch avulsion secondary to surgical embolectomy: management and outcome. Case report.

We report the trans-operative approach and short-term outcome for a patient who suffered a traumatic avulsion of the cilioretinal artery branch during the surgical management of a cilioretinal arterial branch occlusion with intraocular embolectomy. The patient underwent a pars plana vitrectomy with in situ embolectomy. The blocked artery was incised using 25 Ga vertical scissors, and embolus manipulation was performed using microsurgical forceps. During embolus extraction, the occluded cilioretinal artery and its branch were inadvertently avulsed and torn with subsequent intense bleeding. Laser and endodiathermy were used for acute hemostasis. The maneuvers created an unintended retinochoroidal anastomosis. Visual-field improvement was noted three months after the surgery. In the event of a complicated surgical embolectomy with the avulsion of the artery, the formation of a retinochoroidal anastomosis and reperfusion of the occluded artery may occur along with the improvement of the visual field in some cases.

Inverted ILM flap, free ILM flap and conventional ILM peeling for large macular holes.

BACKGROUND: To assess closure rate after a single surgery of large macular holes and their visual recovery in the short term with three different surgical techniques. METHODS: Prospective multicenter randomized controlled trial. We included treatment-naïve patients with diagnosis of large macular hole (minimum diameter of > 400 µm). All patients underwent a comprehensive ophthalmological examination. Before surgery, the patients were randomized into three groups: group A: conventional internal limiting membrane peeling, group B: inverted-flap technique and group C: free-flap technique. All study measurements were repeated within the period of 1 and 3 months after surgery. Continuous variables were assessed with a Kruskal-Wallis test, change in visual acuity was assessed with analysis of variance for repeated measurements with a Bonferroni correction for statistical significance. RESULTS: Thirty-eight patients were enrolled (group A: 12, group B: 12, group C: 14). The closure rate was in group A and B: 91.6%; 95% CI 61.52-99.79%. In group C: 85.71%; 95% CI 57.19-98.22%. There were no differences in the macular hole closure rate between groups (p = 0.85). All groups improved ≈ 0.2 logMAR, but only group B reached statistical significance (p < 0.007). CONCLUSIONS: Despite all techniques displayed a trend toward visual improvement, the inverted-flap technique seems to induce a faster and more significant recovery in the short term.