Macular Hole Surgery and Retinal Tectonics: The Impact of Internal Limiting Membrane Peeling Size on Tangential Retinal Displacement.

PURPOSE: The aim of the study was to evaluate the tangential retinal displacement occurring following macular hole surgery, and to assess the impact of the internal limiting membrane (ILM) peeling size on the extent of the retinal movement. METHODS: This retrospective study included patients with full-thickness macular hole undergoing 25-gauge pars plana vitrectomy with ILM peeling. Patients received either a small ILM peeling with a size of 2-disc diameters or a large peeling extended up to the vascular arcades. Near-infrared retinal imaging was performed with the Spectralis (Heidelberg Engineering, Carlsbad, Germany) before and 6 months after surgery. The tangential retinal displacement was evaluated comparing the optical flow of near-infrared images with a custom digital image analysis algorithm. RESULTS: 44 eyes of 44 patients undergoing vitrectomy with small (n = 24) or large (n = 20) ILM peeling were included. An average overall displacement of 31.3 ± 22.8 µm towards the optic disc was observed after surgery. Large ILM peeling was associated with a significantly higher overall displacement (P = 0.009), displacement in the central 4-mm circle (P < 0.001) and outer 8-mm ring (P = 0.001). Macular holes closure was achieved in 100% and 83.3% of patients in the large and small peeling group, respectively (P = 0.055). CONCLUSIONS: Pars plana vitrectomy with ILM peeling for macular hole results in a tangential retinal displacement towards the optic disc. A larger extent of the ILM peeling leads to a greater tangential movement, possibly improving the macular hole closure rate.

Blue Dye-Assisted Intraoperative Optical Coherence Tomography for Macular Surgery.

INTRODUCTION: The purpose of this study was to evaluate whether vital blue dyes could enhance the contrast of intraoperative optical coherence tomography (OCT) during macular surgery. METHODS: Consecutive patients undergoing elective pars plana vitrectomy for vitreomacular interface disorders were enrolled. Intraoperative OCT was performed with the Artevo 800 microscope (Carl Zeiss Meditec AG, Jena, Germany) before and after injection of 0.2 mL of Trypan Blue and Brilliant Blue G Ophthalmic Solution. The OCT contrast ratio was measured with ImageJ, while the overall scan quality was subjectively classified using a 4-point scale. RESULTS: Ten eyes of 10 patients were enrolled in the study. The OCT contrast ratio was 9.39 ± 5.35 without blue dye and significantly improved to 14.31 ± 10.50 after blue dye injection (p = 0.027). The percentage of patients with a grade 4 scan quality also significantly improved (from 40% without blue dye to 90% with blue dye injection; p = 0.012). CONCLUSION: The use of blue dyes during intraoperative OCT is an effective strategy for improving contrast and scan quality without affecting the surgical time and workflow.

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.

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

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

Pseudodominant inheritance of retinitis pigmentosa in a family with mutations in the Eyes Shut Homolog (EYS) gene.

Sequence variants in Eyes Shut Homolog (EYS) gene are one of the most frequent causes of autosomal recessive retinitis pigmentosa (RP). Herein, we describe an Italian RP family characterized by EYS-related pseudodominant inheritance. The female proband, her brother, and both her sons showed typical RP, with diminished or non-recordable full-field electroretinogram, narrowing of visual field, and variable losses of central vision. To investigate this apparently autosomal dominant pedigree, next generation sequencing (NGS) of a custom panel of RP-related genes was performed, further enhanced by bioinformatic detection of copy-number variations (CNVs). Unexpectedly, all patients had a compound heterozygosity involving two known pathogenic EYS variants i.e., the exon 33 frameshift mutation c.6714delT and the exon 29 deletion c.(5927þ1_5928-1)_(6078þ1_6079-1)del, with the exception of the youngest son who was homozygous for the above-detailed frameshift mutation. No pathologic eye conditions were instead observed in the proband's husband, who was a heterozygous healthy carrier of the same c.6714delT variant in exon 33 of EYS gene. These findings provide evidence that pseudodominant pattern of inheritance can hide an autosomal recessive RP partially or totally due to CNVs, recommending CNVs study in those pedigrees which remain genetically unsolved after the completion of NGS or whole exome sequencing analysis.

The State of Intraoperative OCT in Vitreoretinal Surgery: Recent Advances and Future Challenges.

Since its first introduction more than 30 years ago, optical coherence tomography (OCT) has revolutionized ophthalmology practice, providing a non-invasive in vivo cross-sectional view of the structures of the eye. Mostly employed in the clinical setting due to its tabletop configuration requiring an upright patient positioning, the recent advent of microscope-integrated systems now allows ophthalmologists to perform real-time intraoperative OCT (iOCT) during vitreoretinal surgical procedures. Numerous studies described various applications of this tool, such as offering surgeons feedback on tissue-instrument interactions in membrane peeling, providing structural images in macular hole repair, and showing residual subretinal fluid or perfluorocarbon in retinal detachment surgery. This narrative review aims at describing the state of the art of iOCT in vitreoretinal procedures, highlighting its modern role and applications in posterior segment surgery, its current limitations, and the future perspectives that may improve the widespread adoption of this technology.

The Role of OCT Angiography in the Assessment of Epiretinal Macular Membrane.

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 < 0.05) increase in the superficial capillary plexus vessel density (VD) from baseline to the 6-month follow-up. We observed a large increase in both the perfusion density (PD) and the VD of the deep capillary plexus between baseline and the 6-month follow-up (p < 0.001). A significant decrease in the VD and PD of the choriocapillaris (CC) from baseline to the 1st month and a significant increase in CC perfusion density at the 6-month follow-up compared to the preoperative value were revealed. The FAZ area and perimeter after surgery significantly increased during the follow-up (p < 0.001) at baseline retinal and choroidal plexi with a lower PD or VD correlated with worse visual acuity (p < 0.05 for all plexi). At baseline and at the 1-month follow-up, a significant correlation was found with the FAZ area and the FAZ perimeter: a smaller FAZ area or a smaller FAZ perimeter was correlated to a lower visual acuity. Before surgery, negative correlations (p < 0.05) were found between the Govetto ERM stages and perfusion density of the SCP and the DCP and between the Govetto stages and vessel density of the DCP. CONCLUSIONS: In our study, OCTA detected vascular alterations induced by the presence of the ERM, allowing several correlations with functional data. In these patients, OCTA may be useful to add new potential surgical prognostic factors.

Differential modulation of CXCL8 versus CXCL10, by cytokines, PPAR-gamma, or PPAR-alpha agonists, in primary cells from Graves' disease and ophthalmopathy.

BACKGROUND: Thyrocytes secrete CXC chemokines, particularly (C-X-C motif) ligand (CXCL)8 and CXCL10; its physiopathological significance remains unclear. This study investigates the modulation of the secretion of CXCL8 vs. CXCL10, in human primary cells cultures of thyroid follicular cells (TFC) in Graves' disease (GD), and fibroblasts (OF) or preadipocytes (OP) from Graves' ophthalmopathy (GO). METHODS: Cells were initially incubated with different concentrations of tumor necrosis factor (TNF)α (1, 5, 10 ng/mL). Then, CXCL8 and CXCL10 were measured in the supernatants of TFC, OF or OP cells basally and after 24 h of treatment with interferon (IFN)γ (1000 IU/mL) and/or TNFα (10 ng/mL), in presence/absence of the peroxisome proliferator activated receptor (PPAR)γ agonist pioglitazone (0, 0.1, 1, 5, 10, 20 µM), or the PPARα agonist fenofibrate (5, 10, 50, 100 µM). RESULTS: CXCL8, not CXCL10, was detected in basal conditions in TFC, OF and OP. CXCL8 secretion increased dose-dependently with increasing concentrations of TNFα. CXCL10 secretion was significantly stimulated by IFNγ (P < 0.01) and not by TNFα, whereas CXCL8 was induced by TNFα (P < 0.01), and inhibited by IFNγ (P < 0.01) in TFC, OF and OP. Combining TNFα and IFNγ, the IFNγ-induced CXCL10 secretion was synergistically increased (P < 0.01) while the TNFα-induced CXCL8 secretion (P < 0.01) was reversed in all cell types. Pioglitazone had no significant effect on the secretion of CXCL8 stimulated by TNFα, while inhibited CXCL10. Fenofibrate, in presence of IFNγ plus TNFα, dose-dependently inhibited both CXCL10 and CXCL8 release. CONCLUSION: We first show that TFC, OF, and OP secrete CXCL8 and CXCL10 differentially, sustained by specific proinflammatory cytokines or their combination. This could reflect a different role of the two chemokines in the course of the disease, as CXCL10 could be associated with the initial phase of the disease when IFNγ is preponderant, while CXCL8 could be associated with a later chronic phase of the disease, when TNFα prevails.

Comparison of inverted flap and subretinal aspiration technique in full-thickness macular hole surgery: a randomized controlled study.

PURPOSE: To compare the inverted flap and the subretinal aspiration technique for full-thickness macular hole (FTMH) surgery. METHODS: Forty consecutive eyes with a stage IV FTMH were randomly assigned into 2 treatment groups. After core vitrectomy and perimacular internal limiting membrane (ILM) peeling, in group A, the subretinal remnant macular fluid was aspirated with a 41-G cannula after the air-fluid exchange procedure, while in group B, the technique of an inverted ILM flap was completed. Differences in postoperative best-corrected visual acuity (BCVA) and occurrence of intraoperative or postoperative complications between the 2 groups were evaluated. RESULTS: All FTMHs were closed after the first surgery with no intraoperative or postoperative complications. In group A, 16 patients (80%) showed improvement of BCVA and 4 (20%) showed stabilization. In group B, 12 patients (60%) had improved BCVA, while 6 (30%) remained stable and 2 (10%) worsened. Postoperative BCVA for group A was significantly better than for group B (p = 0.022). CONCLUSIONS: The surgical techniques had similar rates of closure of FTMH, although BCVA outcomes were significantly better in the subretinal aspiration group.

Unilateral Application of Cathodal tDCS Reduces Transcallosal Inhibition and Improves Visual Acuity in Amblyopic Patients.

Objective: Amblyopia is a neurodevelopmental disorder characterized by visual acuity and contrast sensitivity loss, refractory to pharmacological and optical treatments in adulthood. In animals, the corpus callosum (CC) contributes to suppression of visual responses of the amblyopic eye. To investigate the role of interhemispheric pathways in amblyopic patients, we studied the response of the visual cortex to transcranial Direct Current Stimulation (tDCS) applied over the primary visual area (V1) contralateral to the "lazy eye." Methods: Visual acuity (logMAR) was assessed before (T0), immediately after (T1) and 60' following the application of cathodal tDCS (2.0 mA, 20') in 12 amblyopic patients. At each time point, Visual Evoked Potentials (VEPs) triggered by grating stimuli of different contrasts (K90%, K20%) were recorded in both hemispheres and compared to those obtained in healthy volunteers. Results: Cathodal tDCS improved visual acuity respect to baseline (p < 0.0001), whereas sham polarization had no significant effect. At T1, tDCS induced an inhibitory effect on VEPs amplitudes at all contrasts in the targeted side and a facilitation of responses in the hemisphere ipsilateral to the amblyopic eye; compared with controls, the facilitation persisted at T2 for high contrasts (K90%; Holm-Sidak post hoc method, p < 0.001), while the stimulated hemisphere recovered more quickly from inhibition (Holm-Sidak post hoc method, p < 0.001). Conclusions: tDCS is a promising treatment for amblyopia in adults. The rapid recovery of excitability and the concurrent transcallosal disinhibition following perturbation of cortical activity may support a critical role of interhemispheric balance in the pathophysiology of amblyopia.

Mini Drainage Devices for Anterior and Intermediate Filtration.

Mini glaucoma devices for external filtration may be implanted with an ab externo procedure (Ex-PRESS and InnFocus Microshunt) or with an ab interno procedure (XEN Gel stent). The Ex-PRESS is an FDA-approved mini glaucoma device that has been developed in order to simplify anterior guarded filtering procedures, making them faster, safer and easier. It is positioned under a scleral flap and it is introduced in the anterior chamber through a needle hole, avoiding the excision of the corneal-scleral button and the iridectomy. Like other anterior filtering guarded procedures, it may be associated with releasable sutures and with an everting suture (the safe Ex-PRESS procedure) in order to increase safety and efficacy. The InnFocus Microshunt is a new ab externo filtering device currently under investigation; it is very easy to implant and highly promising in terms of safety and efficacy. The XEN Gel stent is an ab interno implanted soft, collagen tube that makes a permanent bypass between the anterior chamber and the subconjunctival space. It is a smart, quick, effective and simple procedure that recently gained FDA approval.

Optical coherence tomography evaluation of patients with macula-off retinal detachment after different postoperative posturing: a randomized pilot study.

PURPOSE: To assess the presence of outer and inner retinal folds (RFs) and drop-out of the ellipsoid zone (EZ) occurring after surgical repair of macula-off rhegmatogenous retinal detachment (RRD) with different postoperative posture and preoperative use of adjuvant perfluorocarbon liquid (PFCO). METHODS: In this prospective study, 56 eyes of 56 consecutive patients affected by RRD were subjected to 23- or 25-gauge pars plana vitrectomy (PPV). The patients were randomized in four groups (14 prone 5 hr without PFCO, 14 supine 5 hr without PFCO, 14 prone 5 hr with PFCO and 14 supine 5 hr with PFCO) and followed up with spectral domain optical coherence tomography (SD-OCT). RESULTS: Spectral domain optical coherence tomography (SD-OCT) was recorded before surgery, at days 30 and 90 to detect the presence of outer RFs, inner RFs and drop-out of EZ and to follow their variation over time. No statistical significance was found in our groups for outer RFs, inner RFs, drop-out of EZ formation and evolution. The postoperative best-corrected visual acuity (BCVA) improved in all groups (mean preoperative BCVA 1.47 logMar ± 0.19, mean postoperative BCVA 0.27 logMar ± 0.11, p < 0.01), without statistical variations between the four groups in BCVA after surgery. CONCLUSION: The use of adjuvant and variation in postoperative position did not change the risk of presenting outer RFs, inner RFs and drop-out of EZ after RRD.

Iatrogenic retinal breaks in ultrahigh-speed 25-gauge vitrectomy: a prospective study of elective cases.

BACKGROUND/AIMS: To evaluate the incidence of intraoperative retinal breaks in the ultrahigh-speed (UHS) 25-gauge vitrectomy system in elective vitreous-retina surgery cases. METHODS: A prospective series of 1676 eyes of 1306 consecutive patients. All eyes underwent an UHS 25-gauge transconjunctival sutureless pars plana vitrectomy for elective cases such as idiopathic epiretinal membrane (586 cases), floaters (153), macular hole (385), vitreous macular traction syndrome (119), dropped nucleus or intraocular lens (84) and vitreous bleeding (82). Patients were followed up for a minimum of 6 months. RESULTS: There were 1409 eyes involved in this study. Iatrogenic retinal breaks were found in 25 eyes (1.8%) during surgery. The majority were detected in cases where posterior vitreous detachment was induced during surgery (21 eyes; 2.8% of the patients), and in only four eyes (0.6%) with an already detached vitreous. In nine cases, rhegmatogenous retinal detachment developed during the follow-up. Patients who showed intraoperative retinal breaks were not in this group. Other complications during the follow-up included two cases of vitreous haemorrhage (0.1%), two cases of dislocated intraocular lens (0.1%), and 23 eyes with hypotony without any further complications. CONCLUSIONS: UHS 25-gauge transconjunctival sutureless vitrectomy is a safe procedure for treatment of elective vitreous-retina cases. The risk of developing iatrogenic breaks seems to be correlated with adhesion of the posterior vitreous hyaloid. Other complications, such as rhegmatogenous retinal detachment or hypotony, were similar to previous reports. No correlation was found between iatrogenic retina breaks and other complications.

Scleral Flap-Everting Suture for Glaucoma-filtering Surgery.

PURPOSE: Most filtering surgery failures develop in the early postoperative period. The possibility to apply an everting suture to lift the flap in the postoperative period and reduce the possibility of an early failure is reported. METHODS: Surgical technique description. RESULTS: An everting suture may be applied to the scleral flap in all types of ab externo anterior filtering surgeries. It could allow the surgeon to lift the scleral flap after the removal of the releasable sutures. CONCLUSIONS: The use of an everting suture would eliminate the need to use procedures for lifting the flap that involve puncturing the conjunctiva and may cause hemorrhages and leakage and promote scarring.

Use of a new intra-ocular spectral domain optical coherence tomography in vitreoretinal surgery.

PURPOSE: To describe the use of a novel intra-ocular side-scanning probe enabling the acquisition of spectral-domain optical coherence tomography (SD-OCT) images during surgery in a series of patients with complex forms of retinal detachment. METHODS: A 23-gauge, side-scanning SD-OCT probe (C7 System; LightLab Imaging, Inc/St Jude Medical, St. Paul, MN, USA) in a 20-gauge catheter, was used to acquire the intra-operative OCT images in seven patients with vitreoretinal diseases. Twenty-five gauge pars plana vitrectomy (PPV) was performed in every patient in a standard fashion. After enlarging the temporal sclerotomy to a 20-gauge port, all the patients were scanned with intra-ocular side-scanning SD-OCT, during different steps of the surgery based on surgeon needs. Scans were recorded real time and directly evaluated on a screen during surgery. Optical coherence tomography (OCT) scans were judged beneficial when they would recognize structures otherwise not seen on biomicroscopy. RESULTS: The intra-ocular SD-OCT has been helpful in acquiring extra information during vitreoretinal surgery such as the detection of the presence of otherwise invisible membranes (epiretinal membrane, subretinal membrane), the location of small tears and the identification of the retinal plane under suboptimal conditions for visualization. CONCLUSION: The use of an intra-ocular SD-OCT can expand upon visual cues during surgery, helping in the decision-making process and allowing additional deliberate surgical manoeuvres aimed at improving surgical outcomes.

Novel Therapies for Thyroid Autoimmune Diseases.

C-X-C chemokine receptor (CXCR)3 and its interferon(IFN)γ-dependent chemokines (CXCL10, CXCL9, CXCL11) are implicated in the immune-pathogenesis of autoimmune thyroiditis (AT), Graves disease (GD) and Graves Ophthalmopathy (GO). In tissue, recruited Th1 lymphocytes produce IFNγ, enhancing the tissue secretion of IFNγ-inducible chemokines, initiating and perpetuating the autoimmune process. Patients with AT (with hypothyroidism), and with GO and GD, particularly in the active phase, have high IFNγ-inducible chemokines. Peroxisome proliferator-activated receptor (PPAR)γ or -α agonists and methimazole exert an immune-modulation on CXCR3 chemokines in AT, GD and GO. Other studies are ongoing to evaluate new molecules acting as antagonists of CXCR3, or blocking CXCL10, in Hashimoto thyroiditis (HT), GD and GO. Recently, novel molecules targeting the various agents involved in the pathogenesis of GO, such as rituximab, have been proposed as an alternative to corticosteroids. However, randomized and controlled studies are needed to generalize these interesting results.

Malignant glaucoma-like syndrome after EX-PRESS filtration surgery.

PURPOSE: To report a case of postsurgical shallow anterior chamber and elevated intraocular pressure (IOP) simulating malignant glaucoma. METHODS: A 20-year-old woman underwent EX-PRESS® device implant for treatment of primary open-angle glaucoma. RESULTS: Postoperative examination showed a shallow anterior chamber, the EX-PRESS® device embedded in the iris, an IOP of 28 mm Hg, and an annular detachment of the choroid ciliary body, suggesting hyperfiltration followed by EX-PRESS® blockage. The anterior chamber was restored using an ophthalmic viscoelastic and an additional suture was applied ensuring the scleral flap. The IOP progressively decreased in the following days and the anterior chamber remained deep and stable. New ocular ultrasonography showed complete resolution of the ciliary body detachment 15 days after surgery. CONCLUSIONS: After glaucoma surgery, not every patient with shallow anterior chamber and normal or high IOP necessarily has a ciliary block glaucoma. In our case, hyperfiltration led to choroidal expansion, shallow anterior chamber, obstruction of the EX-PRESS®, and secondary blockage of outflow. The differential diagnosis is important in order to avoid further invasive procedures (i.e., lensectomy or vitrectomy).

Optical coherence tomography in patients with Chiari I malformation.

BACKGROUND/AIMS: To evaluate optic nerve head with spectral domain optical coherence tomography (OCT) in patients with Chiari I malformation (CMI) compared to healthy controls. METHODS: Cross-sectional study. OCT of the optic nerve head of 22 patients with CMI and 22 healthy controls was quantitatively analyzed. The healthy controls were matched for age and sex with the study population. Mean retinal nerve fiber layer (RNFL) thickness was calculated for both eyes; the mean thickness value was also registered for each quadrant and for each subfield of the four quadrants. RESULTS: CMI patients showed a reduction of the RNFL thickness in both eyes. This reduction was more statistically significant (P < 0.05) for the inferior quadrant in the right eye and in each quadrant than nasal one in the left eye. CONCLUSION: A distress of the retinal nerve fibers could explain the observed reduction of the RNFL thickness in patients with CMI; in our series the reduction of the RNFL thickness seems lower when CMI is associated with syringomyelia.