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Purpose To assess the occurrence of peripheral vitreoschisis-induced vitreous cortex remnants (p-VCRs) in primary rhegmatogenous retinal detachment (RD) and investigate whether the presence of p-VCRs results in a greater risk of RD recurrence, secondary to Proliferative Vitreoretinopathy (PVR) development after pars plana vitrectomy (PPV). Methods Patients who underwent PPV for primary rhegmatogenous RD between January 2016 and December 2018 were included. The presence of residual p-VCRs was confirmed intraoperatively using triamcinolone acetonide (TA). Patients with p-VCRs were divided into two groups: Group A comprised of patients who underwent PPV without p-VCR removal, while Group B included patients who underwent PPV with p-VCR removal. Results Four hundred-thirteen eyes with evidence of p-VCR were analyzed. Two-hundred-twenty-three eyes underwent PPV without VCR removal (Group A), while 190 eyes underwent PPV with p-VCR removal (Group B). Primary anatomical success was 91.5% in the Group A and 95.4% in the group B. Retinal re-detachment due to PVR occurred in 17 (7.6%) eyes in Group A and in four (2.1%) eyes in Group B within the first 3 months (p = 0.01). Among group A, in 11 eyes, there was a diffuse posterior PVR grade C, while six eyes were focal PVR grade C. In Group B, we observed four retinal re-detachment due to focal PVR grade C. Conclusion The presence of p-VCRs seems to be associated with a higher incidence of PVR development and might also result in more complex RD recurrence, this suggests the need for more aggressive VCRs removal during the first surgery.

Purpose To study the post-operative refractive error (RE) of patients undergoing combined phaco-vitrectomy and to find out which intraocular lens (IOL)-power formula had the best refractive outcomes. Methods In this retrospective multicentric study we compared the preoperative expected target with the postoperative RE of patients undergoing combined phaco-vitrectomy due to vitreomacular traction, macular pucker, full thickness macular hole or lamellar macular hole. A multinomial logistic regression was performed to compare the postoperative REs and the differences between expected and postoperative REs among the SRK-T, Olsen's and Holladay-2 formulas. The correlation between the difference in REs and IOL-power was also studied. Results Sixty-seven eyes with a mean axial length of 23.73 ± 1.21 mm were included. Forty-two (63%), 14 (21%) and 11 (16%) eyes were implanted with an IOL that was calculated respectively with SRK-T, Olsen's and the Holladay-2 formula. The mean preoperative expected- and post-operative REs were −0.16 ± 0.12D and −0.48 ± 0.17, respectively ( p = 0.045). SRK-T and Holladay-2 formulas led to a significant myopic shift whereas Olsen's caused a significant hyperopic error, independently from the IOL power. Conclusion Independently from the IOL power, none of the analyzed formulas is precise at calculating the post-operative RE.

Purpose To evaluate the effect of dexamethasone/netilmicin (dexa/net) fixed combination in the treatment of ocular inflammation after sutureless micro-incisional vitreoretinal surgery (MIVS). Patients and Methods This multicenter, open, randomized, active-controlled, parallel-group, clinical trial was run in 6 sites in Italy. Treatment started the day of surgery and continued 4 times daily for 14 days. Patients were 1:1 randomized to dexa/net (eyedrops solution and eye gel) or dexamethasone/tobramycin (dexa/tobra) eyedrops suspension and ointment. Viscous formulations (gel or ointment) were used alone during the early post-operative phase; afterwards, a combination of eye drops during daytime and viscous formulations at bedtime was adopted. The primary efficacy parameter evaluated was bulbar conjunctival hyperemia. Additional efficacy and safety parameters (palpebral conjunctival hyperemia, anterior chamber flare and cells, symptoms of ocular discomfort and ocular tolerance, adverse events and intraocular pressure) were also evaluated. Control visits were performed at day 1, day 4 and day 14 after surgery; the endpoint of the study was set at 14±2 days after surgery. Results A complete resolution of bulbar conjunctiva hyperaemia at the study end point was reached in 92.9% of patients treated with dexa/net and 75.0% of those treated with dexa/tobra (p=0.02, Fisher's exact test). No differences were observed between treatments for other efficacy parameters. Statistically significant differences in favour of dexa/net (p< 0.0001, ANOVA) were observed for most of subjective tolerance variables examined (blurred vision, foreign body sensation, stickiness, burning) starting day 1 after surgery when only the viscous formulations were used. No increase in intraocular pressure or adverse events was observed during the study. Conclusion The combination dexa/net is safe and effective in the treatment of post-operative inflammation following sutureless MIVS. In particular, the use of eye gel formulation is characterized by a great tolerability.

PURPOSE To describe a surgical variant for scleral buckling technique using a chandelier and scleral releasable suture. METHODS We collected retrospectively 20 eyes of 20 patients who underwent to scleral buckling for retinal detachment. In all cases, the surgeons performed the surgical variant of scleral buckling using a 27-gauge (G) chandelier as endoillumination and releasable 7.0 vicryl scleral suture. RESULTS None of the operated eyes developed lens opacity or lens marks at the entrance site of the chandelier used during the surgery, and no cataract development was observed as well, during the follow-up. Retinal reattachment was achieved in 19 out of 20 eyes at the first surgery in the follow-up time of 6 months. CONCLUSION The association of chandelier and releasable suture was a useful surgical variant when performing scleral buckling technique for retinal detachment. Complications like lens opacity or lens marks at the entrance site of the chandelier due to the use of chandelier itself can be greatly reduced, as well as complications due to vitreous prolapse from the sclerotomy by using releasable scleral suture.

Purpose: To assess choriocapillaris vascular density (VD) in healthy and advanced exudative age-related macular degeneration (ae-AMD) patients by new full-range optical coherence tomography angiography (OCT-A). Method: In this observational, cross-sectional study, 21 healthy and 21 ae-AMD eyes, already treated with anti-VEGF, were enrolled. Angio-View retina patterns centered on fovea (6.4 × 6.4 mm) were acquired for all participants using Solix full-range OCT (Optovue Inc., Freemont, CA, USA). The main outcome was to compare choriocapillaris VD between healthy and ae-AMD eyes. Automated measurements of whole image choriocapillaris VD (%) and fovea grid-based (%) were collected for the analysis. Angio-View patterns were used to assess the flow area (mm2) of macular neovascularization (MNV) by contour flow measure algorithm. Best-corrected visual acuity (BCVA) of both groups was also used for the statistical analysis. Results: The mean age was 60.9 (±8.3) in healthy and 73.33 (±15.05) in ae-AMD eyes. The mean BCVA (ETDRS letters) was 98.47 (±1.50) in healthy and 7.04 (±5.96) in ae-AMD eyes. The Mann–Whitney test comparing choriocapillaries VD for whole and fovea healthy and ae-AMD eyes showed statistical significance (p &lt, 0.0001 (t = 4.91, df = 40) and p &lt, 0.0001 (t = 6.84, df = 40), respectively). Regarding, the correlation between MNV and VD of choriocapillaries, neither whole nor fovea areas were statistically significant (F = 0.38 (R2 = 0.01) and 1.68 (R2 = 0.08), respectively). Conclusions: Choriocapillaris VD showed a statistically significant reduction in comparison to healthy eyes in ae-AMD eyes. Choriocapillaris impairment can be seen in the early phase of MNV pathogenesis.

Summary We generated patient-specific disease-free induced pluripotent stem cells (iPSCs) from peripheral blood CD34+ cells and differentiated them into functional endothelial cells (ECs) secreting factor VIII (FVIII) for gene and cell therapy approaches to cure hemophilia A (HA), an X-linked bleeding disorder caused by F8 mutations. iPSCs were transduced with a lentiviral vector carrying FVIII transgene driven by an endothelial-specific promoter (VEC) and differentiated into bona fide ECs using an optimized protocol. FVIII-expressing ECs were intraportally transplanted in monocrotaline-conditioned non-obese diabetic (NOD) severe combined immune-deficient (scid)-IL2rγ null HA mice generating a chimeric liver with functional human ECs. Transplanted cells engrafted and proliferated in the liver along sinusoids, in the long term showed stable therapeutic FVIII activity (6%). These results demonstrate that the hemophilic phenotype can be rescued by transplantation of ECs derived from HA FVIII-corrected iPSCs, confirming the feasibility of cell-reprogramming strategy in patient-derived cells as an approach for HA gene and cell therapy., Graphical Abstract, Highlights • Endothelial cells were differentiated from iPSCs obtained from hemophilic donors • LV transduced-hemophilic endothelial cells secreted FVIII in vitro and in vivo, Follenzi and colleagues show that endothelial cells can be obtained starting from blood CD34+ cells of both healthy and hemophilic donors passing through iPSC generation. During the differentiation process the cells can be genetically modified by LV to express FVIII; corrected endothelial cells secrete FVIII in vitro and ameliorate the hemophilic phenotype in a mouse model of the disease.

Aims To compare the biometric data from partial coherence interferometry (PCI) and swept-source OCT (SS-OCT) in patients with age-related cataract and epiretinal membrane (ERM): ERM, ERM with foveoschisis and macular pseudohole. Methods 49 eyes of 49 subjects including 36 ERM, 9 ERM foveoschisis and 4 macular pseudohole were analysed to evaluate the axial length (AL) measurements and the presence of AL measurement errors, defined basing on the shape of the biometric output graphs and on the concordance of AL values between instruments. Eyes with ERM were divided in four stages according to OCT features (i.e. presence/absence of the foveal pit, presence of ectopic inner foveal layers, disrupted retinal layers). Results The devices provided similar mean AL measurements in all subgroups, with differences Conclusion Both devices provide reliable biometric data in the majority of patients and can be used in the preoperative assessment of patients with age-related cataract and ERM. In eyes with ectopic inner foveal layers, attention should be paid as AL measurement and refractive prediction errors may occur, more frequently with the PCI device.

The failed macular hole is a full-thickness defect involving the fovea that fails to close despite 1 or more surgeries. While many surgical options have been proposed to manage it, none of these guarantee complete anatomical success and satisfactory visual recovery. We report postoperative outcomes on 36 patients affected by failed macular hole, treated with a human amniotic membrane plug transplant. Follow-ups were performed with a standard ophthalmological examination and with advanced multimodal diagnostic imaging. Anatomical closure was achieved at 3 months in all patients. Mean best-corrected visual acuity improved statistically significantly at 6 months (p

Background. The aim of this observational study is to assess pre- and postoperative retinochoroidal vascular changes in patients undergoing epiretinal macular membrane (ERM) surgery by using optical coherence tomography angiography (OCTA). Materials and Methods. 23 eyes affected by ERM and those which underwent phacovitrectomy associated with ERM peeling were enrolled. They were evaluated using structural OCT and OCTA before surgery and at 1, 3, and 6 months postoperatively. Results. We found a statistically significant ( p p p p p

Purpose To study a prototype of an ultrasound-based vitrector, and to try to understand the physical phenomena underlying this new technology. Methods We tested the ultrasound-based vitrector prototype (UV) (ultrasonically-driven handpiece obtained from a modified version of the Alcon CONSTELLATION Vision System [Alcon]) using an automatic experimental setup. Balanced saline solution (BSS) and vitreous (from fresh postmortem enucleated porcine eyes) flow rates were analyzed using three different tips. Results In general, BSS solution flow rates increased with increasing aspiration levels and decreased when we used % US power. Vitreous flow rates were influenced by aspiration levels, % US power, and ultrasound-related phenomena: cavitation phenomenon and "jet streaming." Conclusion Ultrasound-based vitrectomy may represent an important alternative to traditional vitrectomy. Such a tool, capable of liquefying and excising the vitreous body using ultrasound, could overcome all the limits of the guillotine-based technique (GV). Knowledge of the physical phenomena underlying ultrasound-based technology is a necessary prerequisite for further development of this new technology.

PURPOSE Thorough this experimental study, the physic features of a modified 23-gauge vitrectomy probe were evaluated in vitro. METHODS A modified vitrectomy probe to increase vitreous outflow rate with a small-diameter probe, that also minimized tractional forces on the retina, was created and tested. The "new" probe was created by drilling an opening into the inner duct of a traditional 23-gauge probe with electrochemical or electrodischarge micromachining. Both vitreous outflow and tractional forces on the retina were examined using experimental models of vitreous surgery. RESULTS The additional opening allowed the modified probe to have a cutting rate of 5,000 cuts per minute, while sustaining an outflow approximately 45% higher than in conventional 23-gauge probes. The modified probe performed two cutting actions per cycle, not one, as in standard probes. Because tractional force is influenced by cutting rate, retinal forces were 2.2 times lower than those observed with traditional cutters. CONCLUSION The modified probe could be useful in vitreoretinal surgery. It allows for faster vitreous removal while minimizing tractional forces on the retina. Moreover, any available probe can be modified by creating a hole in the inner duct.

(1) Objective: To use optical coherence tomography angiography (OCTA) and microperimetry (MP) to evaluate the correlation between retinal structure and function in patients with idiopathic, full-thickness macular holes (FTMHs) (2) Methods: This prospective, observational study included 11 eyes of 10 patients with FTMHs evaluated before surgery using OCTA and MP. MP sensitivity maps were superimposed and registered on slabs corresponding to superficial capillary plexus (SCP) and deep capillary plexus (DCP) on OCTA, and on the outer plexiform layer (OPL) and the Henle fiber layer (HFL) complex in en face OCT. On these maps, mean retinal sensitivity was calculated at 2&deg, and 4&deg, all centered on the FTMH. Cystic cavity extension was assessed on the slab corresponding to the OPL + HFL complex in en face OCT and DCP in OCTA using the Image J software (Version 1.49v, National Institutes of Health, Bethesda, MD, USA), (3) Results: Absolute scotomas were observed corresponding to the FTMH. Additionally, rings of relative scotoma in the perilesional area were detected and correlated to the cystic spaces on en face OCT and OCTA. There was a significant correlation between reduced retinal sensitivity at 2&deg, diameters around the FTMH and the extension of cystic areas (p &lt, 0.01). There was a significant correlation between the extension of cystic cavities and BCVA (p &lt, 0.01). (4) Conclusions: Morpho-functional analysis of FTMH using OCTA and MP, and the correlation between vascular abnormalities and impaired retinal sensitivity, may provide new, useful information. This integrated evaluation of FTMH may be useful to determine the function&ndash, structure correlation before and after vitreoretinal surgery, in order to gain a better understanding of the functional consequences induced by the morphological alterations, assessing outcomes in a more objective way, and potentially adding new surgical prognostic factors.

Purpose To assess the safety and surgical results of femtosecond laser-assisted phacovitrectomy. Methods Fifteen patients over 50 years of age with coexisting vitreoretinal pathologies and cataract underwent combined femtosecond laser-assisted cataract extraction and sutureless 25-G and 27-G vitreoretinal surgery. Results The indication for surgery was macular hole in 6 patients, epiretinal membrane in 6, vitreous hemorrhage in 2, and retinal detachment in 1. The mean preoperative best-corrected visual acuity (BCVA) was 0.64 ± 0.23 logMAR and the mean postoperative BCVA was 0.19 ± 0.11 logMAR. In 4 patients with epiretinal membrane with corneal astigmatism of 3.35 ± 0.32 D as mean value, a toric intraocular lens (IOL) was implanted: mean residual refractive cylinder was 0.47 ± 0.23 D. Three months postoperatively, mean IOL rotation was 1.64 ± 0.28°. All patients improved their visual acuity. The intraoperative complications of femtosecond laser were 1 subconjunctival hemorrhage, 1 case of miosis, and 1 suction loss. The surgeon was able to maintain a clear view of the retina at all times. After surgery, a better fundus examination was possible with no capsular opacification. Mean follow-up was 6 months. Conclusions Femtosecond laser cataract in vitreoretinal surgery appears a safe and effective technique with potential benefits: the precision and centration of the capsulorhexis may potentially reduce the risk of IOL prolapse into the anterior chamber in gas-filled eyes. Implantation of the toric IOL was effective in reducing preexisting corneal astigmatism and provided good rotational stability and refractive outcome.

PURPOSE Retinal detachment is a frequent complication after removal of silicone oil (ROSO). A retrospective study was conducted to determine whether staining-assisted removal of silicone oil (st-ROSO) allowed better identification and removal of proliferative vitreoretinopathy (PVR) processes compared with a conventional removal of silicone oil technique. METHODS All individuals underwent pars plana vitrectomy (PPV) and silicone oil fill-in for complicated retinal detachments. In conventional removal of silicone oil (Group 1), no staining was used. In staining-assisted removal of silicone oil (Group 2), a mixture of trypan blue and brilliant blue G dyes was used to identify proliferative vitreoretinopathy and subclinical epiretinal membrane. RESULTS After the first 3-month follow-up, 15.9% of patients (N = 608) developed a retinal detachment. Retinal detachment occurred in 22.8% of patients in Group 1 (n = 284) and 9.8% of patients in Group 2 (n = 324; P < 0.001). In Group 2, proliferative vitreoretinopathy removal was performed in 153 eyes (47.2%). CONCLUSION The incidence of retinal redetachment was significantly lower after staining-assisted removal of silicone oil compared with a conventional technique. Staining-assisted removal of silicone oil allowed better identification and removal of proliferative vitreoretinopathy processes.

Francesco Faraldi,1 Vincenzo Papa,2 Daria Rasà,2 Debora Santoro,2 Simona Russo21Struttura Complessa Oculistica III, Presidio Ospedaliero Oftalmico, Torino, Italy; 2Medical Affairs, SIFI SpA, Aci S Antonio, Catania, ItalyPurpose: To compare the efficacy and safety of 0.1% dexamethasone/0.3% netilmicin (Netildex), with that of 0.1% dexamethasone/0.3% tobramycin (Tobradex) in the treatment of external ocular inflammation requiring antibiotic therapy.Methods: In this randomized, double-blind study, 139 subjects with conjunctival inflammation associated with signs of ocular infection were treated with Netildex (n = 71) or Tobradex (n = 68) four times daily for 6 days. The primary efficacy analysis was based on the percentage of patients with at least a 50% decrease in conjunctival hyperemia at the endpoint visit (Day 6 [± 1]) with respect to baseline (responder rate). An equivalence margin of 20% was set for this study. A follow-up visit was performed at Day 14 (± 1). Other efficacy parameters were: conjunctival edema, conjunctival discharge, lid hyperemia, lid edema, presence of ocular infection, and symptoms of ocular discomfort. Safety evaluations included intraocular pressure, visual acuity, and adverse events.Results: At Day 6, a decrease of conjunctival hyperemia was observed in 87.3% and 90.9% of the patients treated with Netildex and Tobradex, respectively. The 95% confidence interval for the difference between groups (–15.3 ÷ 8.0) satisfied the equivalence hypothesis. Subjects treated with Netildex had a better control of lid hyperemia (P = 0.016), tearing (P = 0.001), burning (P = 0.007), and stinging (P = 0.004). No adverse reactions were observed during the study except one case of keratitis in the Tobradex group.Conclusion: Netildex was as effective and safe as Tobradex in reducing signs and symptoms in patients with conjunctival inflammation when ocular infection was suspected.Keywords: conjunctivitis, dexamethasone, netilmicin, red eye

Using manual morphometric techniques, we estimated the amount of neuromelanin in hematoxylin and eosin-stained sections of the pars compacta of the substantia nigra of 19 Alzheimer's patients without nigral Lewy bodies and 12 age-matched controls. Our estimates showed that the mean area and areal fraction of neuromelanin were lower in Alzheimer's disease than controls but the number and size of the neuronal cell bodies, nuclei and nucleoli did not differ between the two groups. We speculated that the decreased amount of neuromelanin in nigral neuronal cell bodies could have resulted from neurofibrillary degeneration, retrograde degeneration from damage of nigral dopaminergic terminals in the striatum by the beta amyloid protein of the diffuse plaques and possibly transneuronal degeneration from damage of cell bodies or dendrites of nigral neurons by their plaque- and tangle-ravaged striatal, neocortical and other subcortical nigral connections. We hypothesized that any or all of the above types of degeneration could have lowered the rate of dopamine metabolism and the formation of one of its by-products, neuromelanin. Our study shows that a decrease in the amount of histopathologically-observable nigral neuromelanin commonly occurs in Alzheimer's disease without nigral Lewy bodies.

The purpose of this review is to stimulate a debate and doubts about future trends in vitreoretinal surgery and social and economic implications. We want to share with our colleagues the challenges of modern ophthalmic surgery in the era of technocratic medicine with the goal to conjugate the technological progress with economic sustainability and equity of access to health facilities and services. The increased possibilities provided by technology result in an increased responsibility. That is, there is no technological imperative, but technology promotes a moral imperative; in particular, it promotes a moral imperative to proper assessment. We offer a historical and economic reappraisal of recent advancements in vitreoretinal surgery since 2002 to today’s state of the art in macular surgery and retinal detachment surgery.

Francesco Faraldi,1 Vincenzo Papa,2 Debora Santoro,2 Daria Rasà,2 Annamaria L Mazza,2 Maria M Rabbione,1 Simona Russo21Department of Ophthalmology III, Presidio Ospedaliero Oftalmico, Torino, Italy; 2SIFI SpA, Catania, ItalyPurpose: The aim of this study was to investigate the effects of an ophthalmic gel containing sodium hyaluronate and xanthan gum in addition to the antibiotic netilmicin in the management of traumatic corneal abrasions.Patients and methods: Patients with traumatic corneal abrasions were randomly treated as follows: Group A (n = 20) with an occlusive patching for 12 hours plus one drop of an eye gel containing 0.15% sodium hyaluronate, 1% xanthan gum and 0.3% netilmicin qid for 5 days; and Group B (n = 20) with an occlusive patching for 2–3 days plus one application of 0.3% netilmicin ophthalmic ointment qid for 5 days. All patients were evaluated after the third and seventh day by slit-lamp examination, fluorescein staining, and corneal defect photograph in order to assess corneal re-epithelialization. Conjunctival hyperaemia, lid oedema, subjective symptoms of discomfort, and conjunctival swabs were also evaluated.Results: No statistically significant difference was observed between the groups in terms of the extent of corneal healing after 3 days of treatment. Both treatments were also highly effective in decreasing the erosion score and the conjunctival hyperemia (P < 0.0001, P < 0.005, respectively) without any significant difference between the two types of treatment. Subjective symptoms of discomfort and conjunctival swabs were also evaluated.Conclusion: In the management of traumatic corneal abrasions, the administration of an eye gel containing sodium hyaluronate and xanthan gum is able to reduce the length of occlusive patching. In addition, the presence of netilmicin guarantees good antibiotic prophylaxis during the wound repair process.Keywords: netilmicin, xanthan gum, wound healing, patching, corneal abrasion