Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

OBJECTIVES: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). METHODS: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. RESULTS: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. CONCLUSION: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY EVALUATION OF PERIPAPILLARY MICROVASCULAR CHANGES AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To evaluate the radial peripapillary capillary plexus (RPCP) vessel density (VD) and the retinal nerve fiber layer (RNFL) thickness in eyes successfully treated with pars plana vitrectomy for primary rhegmatogenous retinal detachment. METHODS: In this cross-sectional multicenter clinical study, eyes with a minimum 12-month follow-up were reexamined. The RPCP VD and RNFL thickness in the rhegmatogenous retinal detachment subfields of the affected eye (study group) were compared with the corresponding areas of the healthy fellow eyes (control group). RESULTS: Fifty-three eyes were included in the study. A significantly lower RPCP VD and RNFL thickness were observed in those subfields affected by rhegmatogenous retinal detachment compared with those of the control group (P < 0.001). No statistically significant differences were observed between undetached subfields in the study group and their corresponding images in the control group. In the study group, a significant correlation was found between RPCP VD and RNFL thickness in subfields with detached retina (r = 0.393, P < 0.001) and undetached retina (r = 0.321, P < 0.001). CONCLUSION: Radial peripapillary capillary plexus VD changes were found in the subfields of detached retina successfully treated with pars plana vitrectomy and they correlated with RNFL thinning. These data suggest a coexistence of neuronal and microvascular damage in patients affected by rhegmatogenous retinal detachment.

Intravitreal Dexamethasone Implant for Postoperative Macular Oedema Secondary to Vitrectomy for Epiretinal Membrane and Retinal Detachment: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the efficacy of intravitreal dexamethasone implant (DEX) for the treatment of macular oedema secondary to vitrectomy for epiretinal membrane (ERM) and retinal detachment (RD) by conducting a systematic review with meta-analysis of published studies. METHODS: Studies reporting clinical outcomes of DEX use for the treatment of macular oedema secondary to ERM and RD vitrectomy were searched on PubMed and Embase databases. The primary outcome was best-corrected visual acuity (BCVA) change between baseline and post-DEX treatment, reported as mean difference (MD) with 95% confidence interval (CI). Mean central macular thickness (CMT) change was assessed as a secondary outcome. Postimplant adverse events, including intraocular pressure rise and cataract development, were reported as well. RESULTS: Five uncontrolled studies, 1 nonrandomized controlled study, and 1 randomized controlled study were included, with a total of 5 cohorts and 3 cohorts in the ERM group and RD group, respectively. Considering the last available follow-up, a significant improvement in postimplant BCVA was found in the overall population, irrespective of the indication for vitrectomy (MD = -0.28, 95% CI = -0.37, -0.20; p < 0.001), but with significant heterogeneity. In either group, mean BCVA significantly improved following the implant (in the ERM group, MD = -0.31, 95% CI = -0.40, -0.22; in the RD group, MD = -0.22, 95% CI = -0.41, -0.03), with no difference between the two groups (p=0.41). However, there was significant heterogeneity in both groups. Considering the last available follow-up, a significant CMT reduction was found in the overall population, irrespective of the indication for vitrectomy (MD = -129.75, 95% CI = -157.49, -102.01; p < 0.001). In the ERM group, a significant CMT reduction was shown following DEX (MD = -133.41, 95% CI = -155.37, -111.45; p < 0.001), with no heterogeneity. In the RD group, mean CMT reduction was borderline significant (MD = -128.37, 95% CI = -253.57, -3.18; p=0.040), with significant heterogeneity. No difference in CMT improvement was found between the two groups (p=0.94). CONCLUSION: This meta-analysis showed that DEX yielded a significant improvement in visual and anatomical outcomes, even if limited by significant heterogeneity. Dexamethasone implant represents an effective treatment for postoperative macular oedema secondary to ERM and RD vitrectomy.

TGF-ß Serum Levels in Diabetic Retinopathy Patients and the Role of Anti-VEGF Therapy.

Transforming growth factor ß1 (TGFß1) is a proinflammatory cytokine that has been implicated in the pathogenesis of diabetic retinopathy (DR), particularly in the late phase of disease. The aim of the present study was to validate serum TGFß1 as a diagnostic and prognostic biomarker of DR stages. Thirty-eight subjects were enrolled and, after diagnosis and evaluation of inclusion and exclusion criteria, were assigned to six groups: (1) healthy age-matched control, (2) diabetic without DR, (3) non-proliferative diabetic retinopathy (NPDR) naïve to treatment, (4) NPDR treated with intravitreal (IVT) aflibercept, (5) proliferative diabetic retinopathy (PDR) naïve to treatment and (6) PDR treated with IVT aflibercept. Serum levels of vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF) and TGFß1 were measured by means of enzyme-linked immunosorbent assay (ELISA). Foveal macular thickness (FMT) in enrolled subjects was evaluated by means of structural-optical coherence tomography (S-OCT). VEGF-A serum levels decreased in NPDR and PDR patients treated with aflibercept, compared to naïve DR patients. PlGF serum levels were modulated only in aflibercept-treated NPDR patients. Particularly, TGFß1 serum levels were predictive of disease progression from NPDR to PDR. A Multivariate ANOVA analysis (M-ANOVA) was also carried out to assess the effects of fixed factors on glycated hemoglobin (HbA1c) levels, TGFß1, and diabetes duration. In conclusion, our data have strengthened the hypothesis that TGFß1 would be a biomarker and pharmacological target of diabetic retinopathy.

Preoperative, Intraoperative and Postoperative Corticosteroid Use as an Adjunctive Treatment for Rhegmatogenous Retinal Detachment.

The treatment for rhegmatogenous retinal detachment (RRD) is surgery, including pars plana vitrectomy (PPV) and scleral buckling (SB). Despite surgical advances, degeneration of the photoreceptors and post-operative complications, such as proliferative vitreoretinopathy (PVR), often occurs as the result of inflammation, preventing complete visual recovery or causing RRD recurrence. There is increasing evidence that in the presence of RRD, the activation of inflammatory processes occurs and the surgery itself induces an inflammatory response. This comprehensive review focuses on the use of different formulations of corticosteroids (CCS), as an adjunctive treatment to surgery, either PPV or SB, for RRD repair. The purpose was to review the efficacy and safety of CCS in improving functional and anatomical outcomes and in preventing postoperative complications. This review is organized according to the timing of CCS administration: preoperative, intraoperative, and postoperative. The evidence reviewed supported the role of the pre-operative use of CCS in the treatment of combined RRD and choroidal detachment (CD), reducing CD height. No solid consensus exists on intraoperative and postoperative use of CCS to treat and prevent postoperative complications. However, a large randomized clinical trial including more than 200 eyes suggested that oral prednisone after surgery decreases the rate of postoperative grade B PVR.

Vascular changes after vitrectomy for rhegmatogenous retinal detachment: optical coherence tomography angiography study.

PURPOSE: To analyse the postoperative foveal avascular zone (FAZ) area, superficial vessel density (SVD) and deep vessel density (DVD) and their correlation with functional (best-corrected visual acuity, BCVA) and anatomical outcomes (foveal macular thickness, FMT) after surgery for rhegmatogenous retinal detachment (RRD) repair. METHOD: Patients with RRD eyes, successfully treated with a single pars plana vitrectomy (PPV) with gas tamponade and a minimum 12 months follow-up, were re-examined. Foveal avascular zone (FAZ) area, SVD, DVD and FMT were evaluated by using optical coherence tomography angiography (OCTA) and compared to fellow eye. RESULTS: Fifty-six patients with macula-on and 37 with macula-off RRD were included in the study. In both groups, no difference in FMT and FAZ area was found compared to fellow eyes. In macula-on RRD eyes, a lower parafoveal DVD (p = 0.001) was detected; FAZ area was related to FMT (p = 0.025), and the postoperative BCVA was correlated with parafoveal DVD (p = 0.010) and FAZ area (p = 0.003). In macula-off RRD eyes, lower parafoveal SDV (p = 0.012), and foveal and parafoveal DVD (p = 0.012 and p < 0.001, respectively) were observed. BCVA was related to FAZ area (p = 0.012), foveal SVD (p = 0.005) and parafoveal DVD (p = 0.010). CONCLUSION: Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower vessel density in the superficial and deep retinal plexus compared to fellow healthy eyes; BCVA was related to FAZ area and vessel density.

Modified Vitrectomy Technique for Phakic Rhegmatogenous Retinal Detachment with Intermediate Break.

PURPOSE: To evaluate the effects of a modification of the traditional 25-gauge pars plana vitrectomy technique in the treatment of uncomplicated macula-on rhegmatogenous retinal detachment (RRD) with intermediate retinal break(s) and marked vitreous traction in the phakic eye. METHODS: Prospective, noncomparative, and interventional case series. All consecutive phakic eyes with primary uncomplicated macula-on RRD with intermediate retinal break(s) and marked vitreous traction, with at least 1 year of postoperative follow-up, were enrolled. In all eyes, "localized 25-gauge vitrectomy" under air infusion with localized removal of the vitreous surrounding the retinal break(s), in association with laser photocoagulation and air tamponade, was performed. The primary end point was the rate of primary retinal attachment. Secondary end points were cataract progression and assessed by digital Scheimpflug lens photography (mean change of nuclear density units) and the rate of complications. RESULTS: Thirty-two phakic eyes were included in the final analysis. At 12 months, the primary outcome of anatomical success was achieved in 94% of eyes. The mean nuclear density units did not change significantly at any time point during the follow-up. After localized vitrectomy, one eye developed an epiretinal membrane, and one eye developed cystoid macular edema; no other significant complications were reported. CONCLUSIONS: "Localized vitrectomy" has a high anatomical success rate in phakic eyes with primary uncomplicated macula-on RRD with intermediate retinal break(s) and marked vitreous traction, without causing progression of cataract.

Surgical management of retinal detachment because of macular hole in highly myopic eyes.

PURPOSE: The purpose of this study was to review the current management of macular hole retinal detachment in highly myopic eyes. METHODS: We searched English MEDLINE databases from January 1997 to January 2011 for surgical management of macular hole retinal detachment in highly myopic eyes. The main outcomes reported include retinal reattachment and visual acuity after primary surgery. RESULTS: Surgical procedures including pneumoretinopexy, pars plana vitrectomy with gas or silicone oil tamponade with or without laser therapy around the macular hole, and macular buckling have been the primary treatment choices. New techniques, including internal limiting membrane or epiretinal membrane peeling and heavy silicone oil tamponade, have been introduced over the last decade, and use of optical coherence tomography has allowed evaluation of the postoperative anatomical status of holes undetectable by conventional ophthalmoscope or lens biomicroscope. Poor functional and anatomical outcomes and nonclosure or reopening of a macular hole are still crucial problems, and some patients may require multiple procedures. CONCLUSION: Macular hole retinal detachment in highly myopic eyes is one of the most difficult types of retinal detachment to treat, and its primary treatment choice is still controversial, although the different surgical techniques reported in this review have been demonstrated as good surgical options. Randomized clinical trials are largely lacking.

Ocular hypotensive effect of oral palmitoyl-ethanolamide: a clinical trial.

PURPOSE: To investigate the effect of oral palmitoyl-ethanolamide (PEA) on intraocular pressure (IOP) in primary open angle glaucoma (POAG) and ocular hypertension (OH). METHODS: In a prospective, randomized, double-blind, crossover clinical trial, 42 patients with POAG or OH who were treated with timolol 0.5% and whose IOP was between 19 and 24 mm Hg received oral PEA (300-mg tablets twice a day) or placebo (PEA vehicle tablets twice a day) for 2 months (period 1), and, after a 2-month washout, received the other treatment for 1 month (period 2). IOP, best-corrected visual acuity, and visual field parameters were considered. RESULTS: After PEA treatment (mean baseline IOP, 21.6 ± 1.7 mm Hg), IOP was reduced by 3.2 ± 1.3 mm Hg at 1 month and by 3.5 ± 1.2 mm Hg (15.9% ± 5.1%) at 2 months (ANOVA, P < 0.001; both Tukey-Kramer, P < 0.01 vs. baseline); after placebo (mean baseline IOP, 21.5 ± 1.5 mm Hg), IOP was reduced by 0.4 ± 1.2 mm Hg at 1 month and by 0.3 ± 1.3 mm Hg at 2 months (t-test at both time points, P < 0.001 vs. PEA). No statistically significant vital signs, visual field, visual acuity changes, or adverse events were detected in either group. CONCLUSIONS: Systemic administration of PEA reduces IOP in patients with glaucoma and ocular hypertension. PEA could be a valuable tool for the treatment of glaucoma (http://www.umin.ac.jp/ctr/index/htm number, UMIN000002833).

Scleral buckle for progressive symptomatic retinal detachment complicating retinoschisis versus primary rhegmatogenous retinal detachment.

OBJECTIVE: To compare the functional and anatomic outcomes of encircling scleral buckle placement for the repair of progressive symptomatic retinal detachment complicating retinoschisis (PSRDCR) with outer-layer breaks (OLBs) posterior to the equator versus primary rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective comparative case series. PARTICIPANTS: Thirty-seven patients with PSRDCR with OLBs posterior to the equator (group A) and 703 patients with primary RRD (group B). METHODS: All eyes were treated with an encircling scleral silicone band (style 240). External drainage of subretinal and retinoschisis cavity fluid and cryopexy or laser photocoagulation around the tears and the OLBs were performed in all eyes. Best-corrected visual acuity at 6 months postoperatively and final retinal reattachment rate were analyzed. RESULTS: There was no statistically significant difference between the 2 groups in terms of patient age, gender, percentage of retinal detachments that were macula-off (p = 0.241), and preoperative best-corrected Snellen visual acuity (p = 0.927). Best-corrected Snellen visual acuity at 6 months postoperatively was < or =20/100 in 35% of eyes, 20/100-20/50 in 14% of eyes, and > or =20/40 in 51% of eyes in group A versus > or =20/100 in 37% of eyes, 20/100-20/50 in 33% of eyes, and > or =20/40 in 30% of eyes in group B (p = 0.12); the final retinal reattachment rate was 97% in group A versus 98% in group B (p = 0.77). CONCLUSIONS: Placement of an encircling scleral buckle may be an effective method to manage both PSRDCR with OLBs posterior to the equator and primary RRDs. The procedure is associated with comparable visual acuity and anatomic outcomes for both types of retinal detachment.

Keratoconus staging: a computer-assisted ultrabiomicroscopic method compared with videokeratographic analysis.

PURPOSE: The aim of this study was to introduce a new paradigm for keratoconus assessment, the keratoconus index (KI), generated from the ratio of peripheral corneal thickness (PCT) to the thinnest corneal thickness (TCT), and calculated by a computer-assisted procedure after ultrabiomicroscope (UBM) examination. Then we compared KI and the keratoconus severity index (KSI), obtained by videokeratography in patients with different stages of keratoconus. METHODS: We studied 60 eyes with different forms of keratoconus using the TMS-3 autotopographer, provided with a keratoconus screening program (using Smolek-Klyce methods) and the commercial version of the ultrasound biomicroscope (Paradigm UBM Plus Model P45) equipped with a 50-MHz probe, which was provided with our computer-assisted program. The proportion test Z and the correlation coefficient R were applied to the outcomes. RESULTS: The keratoconus severity index, KSI, obtained by color-coded videokeratographic maps, was in the range 95% to 32% (mean 52.22%). By means of UBM examination, we obtained 60 images and found values of TCT 0.278-0.592 mm and PCT 0.475-0.704 mm. Applying the computer-assisted method, we obtained values for KI of 1.112-2.159 (mean 1.428). CONCLUSIONS: KI is correlated as well as KSI with the severity of the keratoconus (R = 0.76, P < 0.0001). It can be used as a similar parameter to measure the evolution of the disease, on the basis of corneal thickness rather than the curvature.