Purtscher-like retinopathy in a patient with systemic tacrolimus vasculopathy.

INTRODUCTION: Purtscher-like retinopathy is a rare occlusive retinal microangiopathy, whose pathogenesis has not been totally defined yet. Most frequent cause of Purtscher-like retinopathy is acute pancreatitis, but it may be triggered by other systemic or toxic conditions. We report herein a case of Purtscher-like retinopathy in the context of systemic tacrolimus vasculopathy. CASE REPORT: A 56-years old male with history of kidney transplant was referred to local emergency room because of a global worsening of health conditions, with fatigue, muscular pain and diuresis contraction. During hospitalization the patient came to our attention for sudden and severe visual acuity impairment in both eyes. Extensive ophthalmological assessment, optical coherence tomography (OCT) and fluorescein angiography (FA) were performed disclosing a marked drop in best corrected visual acuity (BCVA) (20/200 in the right eye and 10/400 in the left eye) caused by a bilateral severe occlusive retinal microangiopathy complicated by diffuse retinal ischaemia and neovascular glaucoma. Muscular biopsy showed a necrotizing myopathy with autoimmune features, as indicated by conspicuous upregulation of MHC-I complex and microangiopathic changes, consistent with tacrolimus toxicity. Tacrolimus administration was interrupted, and intravenous glucocorticoids were administered. The large areas of retinal ischemia and neovascular glaucoma were treated with pan-retinal photocoagulation and intravitreal injections of bevacizumab with complete regression of iris neovascolarization. BCVA measured 20/200 in both eyes at last follow-up visit, 20 months after symptoms onset. CONCLUSIONS: Purtscher-like retinopathy should be suspected in patients under treatment with calcineurin inhibitors especially in case of sudden and severe bilateral visual impairment.

Vitreomacular interface alterations following peripheral laser retinopexy: Interface changes after laser.

AIM: To demonstrate the morphological outcomes of macular hole following prophylactic peripheral laser retinopexy (PPLR). METHODS: Our retrospective case-control analysis included 92 eyes, 55 in the laser group and 37 in the non-laser group. Fifty-five patients were subjected to prophylactic peripheral laser retinopexy in preparation for pars plana vitrectomy for macular hole, with and without vitreomacular adhesion (laser group). Before and after prophylactic peripheral laser retinopexy, we evaluated any changes in vitreomacular anatomy by optical coherence tomography. Optical coherence tomography changes were also analyzed in the visits preceding pars plana vitrectomy in 37 macular hole eyes not subjected to prophylactic peripheral laser retinopexy (non-laser group). RESULTS: In the laser group, 7 out of 55 eyes (12.7%) showed macular hole closure (6 out of 18 macular hole eyes with vitreomacular adhesion (33.3%) and 1 out of 37 eyes without vitreomacular adhesion (2.7%)), while no patients showed macular hole closure in the non-laser group (p < 0.05). The mean width of the seven closed macular hole was 191.4 µm (range: 59-282 µm). In all except one of the six macular hole eyes with vitreomacular adhesion, the macular hole closed without vitreomacular adhesion release. In our analysis of the patient subgroup with vitreomacular adhesion, we observed a release of vitreomacular adhesion in 3 out of 18 eyes (16.6%) in the laser group and in 1 out of 13 eyes (7.6%) in the non-laser group (p > 0.05). CONCLUSION: These findings support a possible beneficial role for prophylactic peripheral laser retinopexy in selected individuals with macular hole.

Long-term evaluation of corneal sub-basal nerve recovery after photorefractive keratectomy and influence of pars plana vitrectomy.

The corneal sub-basal nerve (SBN) plexus is destroyed during photorefractive keratectomy (PRK) and its recovery is still a matter of debate. In vivo confocal microscopy (IVCM) was used to evaluate SBN plexus in 23 patients at a distance of 10-25 years (mean 15.6 years) from myopic PRK. Because 8 out of the 23 PRK patients underwent pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment, IVCM was also performed on those patients 6 months after PPV. Thirteen patients matched for age and myopia served as controls (non-PRK). SBN plexus was markedly reduced after PRK compared with non-PRK eyes and showed a slow, continuous but incomplete recovery up to the end of our follow-up (range 10-25 years). PRK and non-PRK eyes showed a marked reduction in SBN density 6 months after PPV, thus demonstrating a detrimental effect exerted by PPV on SBN plexus.

Corneal Subbasal Nerve Density and Sensitivity After Pars Plana Vitrectomy Using Contact or Noncontact Wide-Angle Viewing Systems.

PURPOSE: To assess corneal subbasal nerve density (SBND) and corneal sensitivity (CS) after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) without intraoperative 360-degree laser treatment using contact or noncontact panoramic viewing systems. METHODS: This is a prospective study of 34 eyes affected by RRD, which underwent PPV using contact (18 eyes) and noncontact (16 eyes) panoramic viewing systems; 12 eyes which underwent scleral buckling, and 17 eyes which underwent cataract surgery. SBND and CS were assessed before surgery and 3 and 6 months postoperatively by in vivo confocal microscopy and Cochet-Bonnet esthesiometry. RESULTS: Compared with baseline values, at 6 months, SBND and CS decreased in both contact PPV (SBND preoperative value: 19.1 ± 3.7 mm/mm; SBND postoperative value: 3.5 ± 1.3 mm/mm; CS preoperative value: 5.1 ± 0.5 cm; CS postoperative value: 1.5 ± 0.4 cm) and in noncontact PPV groups (SBND preoperative value: 19.5 ± 3.8 mm/mm; SBND postoperative value: 8.7 ± 2.3 mm/mm; CS preoperative value: 5.3 ± 0.5 cm; CS postoperative value: 2.5 ± 0.7 cm) (P < 0.001 for all comparisons). SBND reduction was greater in the contact PPV group than in the noncontact PPV group (P < 0.001). By contrast, the scleral buckling and cataract surgery group values were unchanged (P > 0.1 for all comparisons). In multivariate analysis, no significant effect was found for cataract surgery associated with PPV, pseudophakia, surgical time, intraocular pressure, or for laser in horizontal sectors for PPV groups. SBND was highly correlated with CS (r = 0.93). CONCLUSIONS: A contact viewing system reduces SBND after PPV more than a noncontact system does.

Publisher Correction: TGF-ß concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration.

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TGF-ß concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration.

Controversy still exists regarding the role of the TGF-ß in neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Here, we measured the concentrations of active TGF-ß1, TGF-ß2, and TGF-ß3 by ELISA in the aqueous humor of 20 patients affected by nAMD, who received 3 consecutive monthly intravitreal injections of anti-VEGF-A antibody. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). The same samples were used in a luciferase-based reporter assay to test the TGF-ß pathway activation. Active TGF-ß1 concentrations in the aqueous humor were below the minimum detectable dose. Active TGF-ß2 concentrations were significantly lower at baseline and at month 1, compared to controls. No significant differences in active TGF-ß3 concentration were found among the sample groups. Moreover, TGF-ß pathway activation was significantly lower at baseline compared to controls. Our data corroborate an anti-angiogenic role for TGF-ß2 in nAMD. This should be considered from the perspective of a therapy using TGF-ß inhibitors.

VITREOUS INCARCERATION IN SCLEROTOMIES AFTER VALVED 23-, 25-, OR 27-GAUGE AND NONVALVED 23- OR 25-GAUGE MACULAR SURGERY.

PURPOSE: To study the patterns of vitreous incarceration at sclerotomy sites by ultrasound biomicroscopy in patients subjected to valved or nonvalved small-gauge pars plana vitrectomy. METHODS: A prospective comparative study of 88 eyes affected by epiretinal membrane and macular hole. Patients were divided into four groups: valved or nonvalved 23-gauge (16 eyes each) and valved or nonvalved 25-gauge (20 eyes each); their vitreal disposition was compared by ultrasound biomicroscopy. Vitreal disposition was also assessed in 16 eyes of 16 patients subjected to valved 27-gauge pars plana vitrectomy. RESULTS: Three vitreal patterns were identified: P0 (vitreous not visible or vitreous strand distant from the sclerotomy site), P1 (vitreous strand parallel to and in contact with the sclerotomy site), and P2 (vitreous strand entrapped in the sclerotomy site). The effect of valved trocar use on vitreous incarceration seemed to be somewhat beneficial, but no statistically significant effect could be shown (odds ratio: 0.85, 95% confidence interval: 0.42-1.74, P = 0.657). Similarly, no differences in vitreous incarceration were shown among vitrectomy gauges (23, 25, or 27) both in a model including valved trocars only (P = 0.858) and in a model with all available data (P = 0.935). CONCLUSION: In 23- and 25-gauge macular surgeries, postoperative vitreous incarceration does not seem to be reduced using valved cannulas and was similar to that observed in 27-gauge surgery.

HTRA1 and TGF-ß1 Concentrations in the Aqueous Humor of Patients With Neovascular Age-Related Macular Degeneration.

Purpose: The purpose of this study was to evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), TGF-ß1, bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and VEGFA proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to AMD. Methods: We measured by ELISA the concentrations of HTRA1, TGF-ß1, BMP4, GDF6, and VEGFA in the aqueous humor of 23 patients affected by nCNV who received three consecutive monthly intravitreal injections of 0.5 mg ranibizumab. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). Twenty-three age-matched cataract patients served as controls. Results: Bone morphogenetic protein 4 and GDF6 were not detectable in any samples. Baseline HTRA1 was higher than controls (P < 0.0001) and higher than both the month 1 (P < 0.0001) and the month 2 (P < 0.0001) values. Baseline VEGFA was higher than controls (P < 0.0001), not different from month 1 value (P = 0.0821), but higher than month 2 value (P < 0.0001). Baseline TGF-ß1 was higher than controls (P = 0.0015) and not different from month 1 (P = 0.129) and month 2 values (P = 0.5529). No correlation was found in naïve patients between concentrations of HTRA1 and TGF-ß1, HTRA 1 and VEGFA, or TGF-ß1 and VEGFA. Conclusions: In nCNV patients, HTRA1 and TGF-ß1 were significantly higher compared to controls. After treatment, TGF-ß1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-ß1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-ß1.

CD93 as a Potential Target in Neovascular Age-Related Macular Degeneration.

In patients with age-related macular degeneration (AMD), choroidal neovascularization is the major cause of severe visual loss. In these patients, the persistence of neovascular growth despite vascular endothelial growth factor-A blockage needs the discovery of new endothelial cell targets. The glycoprotein CD93, highly expressed in activated endothelial cells, has been recently involved in the regulation of the angiogenic process both as transmembrane and soluble protein. Choroidal neovascular membranes from patients affected by AMD were examined by immunofluorescence using anti-CD93 and anti-von Willebrand factor antibodies. Blood vessels within intraocular and extraocular neoplasias were used as controls for CD93 expression. All choroidal neovascular membranes displayed strong CD93 staining in the von Willebrand factor-positive endothelial cells, consistently with the analyses showing a high colocalization coefficient in the blood vessels. Intraocular and extraocular tumor vessels showed similar results, whereas the normal choroid displayed blood vessels with only faint CD93 staining. Additionally, the concentration of soluble CD93 was determined in the aqueous humor of patients affected by naïve neovascular AMD by enzyme-linked immunosorbent assays. Age-matched cataract patients served as controls. Soluble CD93 was significantly increased in the aqueous humor of naïve neovascular AMD patients and tended to decrease after treatment with an antiangiogenic drug. In conclusion, both transmembrane and soluble CD93 are overexpressed in patients with neovascular AMD, indicating that CD93 may represent a potential new antiangiogenic target in the treatment of choroidal neovascularization. J. Cell. Physiol. 232: 1767-1773, 2017. © 2016 Wiley Periodicals, Inc.

COMPLEX RETINAL DETACHMENT IN PHAKIC PATIENTS: Previtrectomy Phacoemulsification Versus Combined Phacovitrectomy.

PURPOSE: To assess the impact of phacoemulsification performed one week before pars plana vitrectomy versus combined phacovitrectomy on postoperative anterior segment status and final functional and anatomical outcomes in phakic patients affected by complex rhegmatogenous retinal detachment. METHODS: The authors retrospectively reviewed the records of 59 phakic patients affected by complex rhegmatogenous retinal detachment. Twenty-nine patients underwent cataract surgery 7 days before vitrectomy (preemptive cataract surgery-Group 1), whereas 30 patients underwent combined phacovitrectomy (Group 2). Preoperative, intraoperative, early- and late-postoperative outcomes were measured and compared. RESULTS: Numbers of previous retinal surgical procedures, nuclear sclerosis grade, proliferative vitreoretinopathy grade, eyes with inferior breaks, surgical time, and ratio of silicone oil/gas tamponade were all similar between the two groups. After surgery, there was less extension of posterior synechia in Group 1. There was no significant difference in fibrin, number of patients with posterior synechia, final intraocular pressure, retinal redetachment rate, final retinal status, or final best-corrected visual acuity. CONCLUSION: Preemptive cataract surgery was associated with less extensive postoperative posterior synechia, however, its final functional and anatomical outcomes were not significantly different from those of phacovitrectomy. Both approaches were efficacious.

The Incidence of Rhegmatogenous Retinal Complications in Macular Surgery After Prophylactic Preoperative Laser Retinopexy: A Retrospective Study.

The aim of the study is to evaluate the clinical characteristics of intraoperative retinal breaks (RBs) and postoperative retinal detachment (RRD) in patients undergoing pars plana vitrectomy (PPV) for macular disorders, who were treated preoperatively with prophylactic peripheral laser retinopexy.This observational cohort study comprised of 254 patients who underwent macular surgery and were preoperatively subjected to prophylactic laser retinopexy anterior to the equator. The main outcome measures were the incidence and characteristics of intraoperative RBs and postoperative RRD.Intraoperative RBs occurred in 14 patients (5.5%). Ten patients presented a sclerotomy-related RB (3.9%) and 4 patients a nonsclerotomy-related RB (1.6%). Two patients showed postoperative RRD (0.7%). Neither of the 2 patients with postoperative RRD was macula-off at presentation: one of them was successfully operated on with scleral buckling and the other was managed by observation alone. A significantly increased risk for the intraoperative development of sclerotomy-related RB was found in 20-gauge PPV compared with 23/25-gauge PPV.Preoperative prophylactic peripheral laser retinopexy does not guarantee the prevention of intraopertaive RBs or postoperative RRD. However, it might prevent the involvement of the macula when RRD occurs postoperatively.

Corneal Complications During and After Vitrectomy for Retinal Detachment in Photorefractive Keratectomy Treated Eyes.

To evaluate the occurrence of late-onset corneal haze (LOCH) after vitrectomy for rhegmatogenous retinal detachment (RRD) in photorefractive keratectomy (PRK)-treated eyes. This observational cohort study comprised 13 eyes of 13 patients who underwent vitrectomy for RRD and who had been subjected to PRK years earlier. The occurrence of LOCH was evaluated together with all the preoperative, intraoperative, and postoperative factors that could affect final corneal status. LOCH developed in 2 eyes. Both patients had undergone PRK for high myopia--one 3 years and the other 9 years prior to RRD. Both patients presented with RRD due to giant retinal tear and were subjected to scleral buckle, 20-gauge vitrectomy, and silicone oil tamponade. Three months after vitrectomy and 1 month after silicone oil removal they both developed LOCH. During vitreoretinal surgery neither of the 2 patients needed mechanical epithelial debridement. Intraoperative epithelial debridement was performed in 2 of the other patients of the series, who had undergone previous PRK for high myopia and had clear corneas at presentation; in 1 of them this manoeuvre hampered intraoperative visualization. Follow-up after retinal detachment surgery ranged from 6 to 156 months (mean, 37.5 months). Subepithelial corneal scarring may be reactivated many years after PRK. In our series this happened after vitrectomy.

Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization.

PURPOSE: To evaluate the long-term efficacy of bevacizumab in the treatment of choroidal neovascularization (CNV) secondary to pathological myopia. METHODS: In this retrospective single-center non-comparative study the medical records of 29 eyes from 29 patients with naïve CNV secondary to high myopia and at least 42 months of follow up were reviewed. All eyes received a loading dose of one intravitreal injection per month for two consecutive months and were retreated on an as-needed basis during the course of follow up. The main outcome measures were post-treatment ETDRS best-corrected visual acuity (BCVA) and visual stabilization over time. Stepwise linear regression analysis was performed to identify prognostic factors for visual acuity gain and final visual acuity outcome at 42 months. RESULTS: At 42 months of follow-up bevacizumab was associated with the maintenance of significant benefits in visual acuity compared to baseline. No adverse ocular or systemic effects from treatment were encountered. No statistically significant correlations were found between BCVA change and any of the quantitative variables. However, when final BCVA was taken as a dependent variable and CNV size and pre-treatment VA were included as predictors, a bivariate model was identified by stepwise regression which gave a 75 % of explained variance. CONCLUSIONS: Bevacizumab treatment was found to be efficacious in the treatment of myopic CNV, resulting in stable gains in visual acuity lasting at least 42 months, without any adverse ocular or general events. Myopic CNV size was identified as a significant prognostic factor.

Capsule contraction syndrome with a microincision foldable hydrophilic acrylic intraocular lens: two case reports and review of the literature.

Here we present 2 cases of capsule contraction syndrome (CCS). In both cases, a hydrophilic acrylic Akreos MI60 (Bausch and Lomb) intraocular lens (IOL) was implanted in the capsular bag through microincision cataract surgery, and the literature on the subject is reviewed. Since CCS has been described after the implantation of every IOL type, it is unlikely that the Akreos MI60 chemical and physical properties may cause CCS. When CCS occurs with IOLs composed of increasingly flexible materials that are inserted through incisions of decreasing size, a severe dislocation and deformation of IOL optics and haptics may develop. In both cases illustrated here, Nd:YAG laser anterior capsulotomy was highly effective. Hence, also based on the literature, which reports severe complications as a result of surgical intervention, it is suggested that Nd:YAG laser anterior capsulotomy be the first line of CCS treatment when the luxation of an IOL capsular bag is absent.

Impact of intraoperative topical hydroxypropyl methylcellulose 2% versus sodium hyaluronate 1.2% on corneal reepithelialization after intentional epithelial debridement during vitrectomy.

PURPOSE: The aim of this study was to assess the impact of the intraoperative use of topical hydroxypropyl methylcellulose (HPMC) 2% versus sodium hyaluronate 1.2% on corneal reepithelialization time and final corneal status after intentional epithelial debridement during vitrectomy for proliferative vitreoretinopathy. METHODS: Forty eyes of 40 patients were included in the study, divided into 2 groups of 20 eyes. HPMC 2% and sodium hyaluronate 1.2% were used as corneal protectors in the first and second group, respectively. Patients' charts were reviewed to determine any differences between the HPMC 2% and sodium hyaluronate 1.2% groups in relation to the preoperative, intraoperative, and postoperative factors that could impact postoperative corneal reepithelialization. Postoperative reepithelialization time and final corneal status were recorded. RESULTS: No significant between-group differences in preoperative, intraoperative, and postoperative factors were found. Reepithelialization time was significantly shorter in the sodium hyaluronate 1.2% group than in the HPMC 2% group, although reepithelialization was eventually achieved in every patient in both groups. Corneal sequelae were significantly more frequent in the HPMC 2% group than in the sodium hyaluronate 1.2% group. CONCLUSIONS: The choice of the ophthalmic viscosurgical device for intraoperative corneal protection may significantly influence the postoperative corneal status after complicated retinal detachment.

Disease pathways in proliferative vitreoretinopathy: an ongoing challenge.

Despite remarkable advances in vitreoretinal surgery, proliferative vitreoretinopathy (PVR) remains a common cause of severe visual loss or blindness. One of the critical reasons for PVR-induced blindness is tractional retinal detachment due to the formation of contractile preretinal fibrous membranes. This membrane formation is characterized by the proliferation and migration of cells and the excessive synthesis and deposition of extracellular matrix proteins. Herein we present the disease pathways of PVR, reviewing the role of both systemic and intraocular cells as well as molecular mediators. A chronological sequence of events leading to PVR is also hypothesized. Better understanding of the pathogenesis of PVR is needed in order to improve disease management. Efforts should be oriented towards greater cooperation between basic researchers and clinicians, aimed at matching the different clinical scenarios with the biological markers of the disease.

F6H8 as an Intraoperative Tool and F6H8/Silicone Oil as a Postoperative Tamponade in Inferior Retinal Detachment with Inferior PVR.

Purpose. To evaluate the effectiveness and safety of perfluorohexyloctane (F6H8) for intraoperative flattening of the retina and of F6H8/silicone oil (SO) 1000 cSt as a postoperative tamponade for inferior retinal detachment with inferior proliferative vitreoretinopathy. Methods. This is a retrospective review of 22 patients who underwent pars plana vitrectomy using F6H8 as an intraoperative tool to flatten the retina. At the end of the surgery a direct partial exchange between F6H8 and SO 1000 cSt was performed, tamponing the eye with different ratios of F6H8/SO (70/30, 60/40, 50/50, 40/30, and 30/70). Anatomical and functional results and complications were evaluated over the follow-up period (mean 22.63 months). Results. F6H8 was efficacious for intraoperative flattening of the retina. Twenty-one of the 22 patients achieved a complete retinal reattachment. Postoperative visual acuity (VA) ranged from light perception to 20/70, with 72% of patients obtaining VA better than 20/400. No emulsification/inflammation was observed whatever the ratio of F6H8/SO used. With higher ratios of F6H8/SO (70/30 and 60/40) cloudiness of the tamponade was observed. A transparent mixture was present with all the other ratios. Conclusions. The surgical technique adopted is very simple and safe. The optimal F6H8/SO ratio seems to be between 50/50 and 30/70.

Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results.

PURPOSE: To assess the clinical results of transepithelial collagen crosslinking (CXL) in patients 26 years and younger with progressive keratoconus suitable for epithelium-off (epi-off) CXL. SETTING: Department of Ophthalmology, Siena University Hospital, Siena, Italy. DESIGN: Prospective case series. METHODS: The study included 26 eyes (26 patients) treated by transepithelial (epithelium-on) CXL. The mean age was 22 years (range 11 to 26 years) (10 younger than 18 years; 16 between 19 years and 26 years). Preoperative and postoperative examinations included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, simulated maximum keratometry (K), coma and spherical aberration, and corneal optical coherence tomography optical pachymetry. The solution for transepithelial CXL (Ricrolin TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet-A treatment was performed with the Caporossi Baiocchi Mazzotta X Linker Vega at 3 mW/cm(2). RESULTS: After relative improvement in the first 3 to 6 months, the UDVA and CDVA gradually returned to baseline preoperative values. After 12 months of stability, the simulated maximum K value worsened at 24 months. Coma aberration showed no statistically significant change. Spherical aberration increased at 24 months. Pachymetry showed a progressive, statistically significant decrease at 24 months. Fifty percent of pediatric patients were retreated with epi-off CXL due to significant deterioration of all parameters after 12 months of follow-up. CONCLUSIONS: Functional results after transepithelial CXL showed keratoconus instability, in particular in pediatric patients 18 years old and younger; there was also functional regression in patients between 19 years and 26 years old after 24 months of follow-up. mentioned.