Relaxing Retinotomy in Recurrent and Refractory Full-Thickness Macular Holes: The State of the Art.

The prevailing standard of care for primary repair of full-thickness macular holes (FTMHs) is pars plana vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade, as it gives a high closure rate of roughly 90%. On the other hand, the surgical management of recurrent and refractory FTMHs represents, so far, a demanding and debated subject in vitreoretinal surgery since various approaches have been proposed, with no consensus concerning both adequate selection criteria and the best surgical approach. In addition, the existence of multiple case series/interventional studies showing comparable results and the lack of studies with a direct comparison of multiple surgical techniques may lead to uncertainty. We present an organized overview of relaxing retinotomy technique, a surgical approach available nowadays for the secondary repair of recurrent and refractory FTMHs. Besides the history and the description of the various techniques to perform relaxing retinotomies, we underline the results and the evidence available to promote the use of this surgical approach.

CONVENTIONAL INTERNAL LIMITING MEMBRANE PEELING VERSUS INVERTED FLAP FOR SMALL-TO-MEDIUM IDIOPATHIC MACULAR HOLE: A Randomized Trial.

PURPOSE: To compare conventional internal limiting membrane (ILM) peeling versus inverted flap technique in small-to-medium idiopathic macular hole. METHODS: Eyes with ≤400 µ m idiopathic macular holes were randomized into the conventional ILM peeling group (25 eyes) and inverted flap group (25 eyes). A 12-month follow-up was considered. Macular sensitivity (MS) change detected with MP-1 microperimetry was the primary outcome. Secondary outcomes included best-corrected visual acuity change, closure rate, anatomical findings on optical coherence tomography such as U-shape foveal contour, restoration of external limiting membrane, and ellipsoid zone. RESULTS: In both groups, MS improved throughout the follow-up. Final MS was greater in the conventional ILM peeling group compared with the inverted flap group, being 16.6 ± 2.3 dB versus 14.9 ± 2.9 dB, respectively ( P = 0.026). In both groups best-corrected visual acuity improved throughout the follow-up, with a final best-corrected visual acuity of 0.19 ± 0.14 logMar (20/31 Snellen) in the conventional ILM group and 0.22 ± 0.11 logMar (20/33 Snellen) in the inverted flap group ( P = 0.398). Anatomical hole closure was achieved in all cases. No difference in optical coherence tomography findings was shown between the two groups. CONCLUSION: A better final MS was found in eyes undergoing conventional ILM peeling. Inverted flap technique has disadvantages compared with conventional peeling for the treatment of small-to-medium idiopathic macular holes.

Reintervention rate in glaucoma filtering surgery: A systematic review and meta-analysis.

PURPOSE: Reintervention rate is an important factor impacting on patients, surgeons, and society. To date, only a few studies have focused on this topic. For this reason, a systematic review and meta-analysis was undertaken to assess the reintervention rate after glaucoma filtering surgery. MATERIALS AND METHODS: Prospective studies reporting the reintervention rate after glaucoma filtering surgery and with at least 12 months of follow-up were systematically searched on PubMed, Medline and Embase databases. The primary outcome was the total reintervention rate following surgery. Secondary outcomes were: the rate of manipulation, in-clinic and in-operating room reintervention; the reintervention rate for intraocular pressure (IOP) control and for complications; demographic, clinical and surgical variables associated with reintervention rate. RESULTS: Ninety-three studies with a total of 8345 eyes were eligible. The total reintervention rate was 1.84 (95% CI 1.57-2.13), with a lower rate for Baerveldt (0.53, 95% CI 0.29-0.83) and Preserflo (0.60, 95% CI 0.15-1.29), and a higher rate for Xen (4.26, 95% CI 2.59-6.31). The manipulation rate was 0.99 (95% CI 0.77-1.23), the in-clinic reintervention rate was 0.08 (95% CI 0.05-0.12) and the in-operating room reintervention rate was 0.28 (95% CI 0.22-0.35). The reintervention rate for IOP control was 1.26 (95% CI 1.04-1.51) and the reintervention rate for complications was 0.27 (95% CI 0.21-0.35). CONCLUSIONS: All types of surgery presented a total reintervention rate similar to the overall findings, except studies on Baerveldt and Preserflo Microshunt, with a lower rate, and Xen, with a higher rate. None of the variables evaluated were found to be directly associated with the explored outcomes.

Epiretinal Membrane Vitrectomy With and Without Intraoperative Intravitreal Dexamethasone Implant: A Systematic Review With Meta-Analysis.

Purpose: To evaluate the efficacy of vitrectomy combined with intravitreal dexamethasone implant vs. vitrectomy without the implant in patients with epiretinal membrane (ERM) by conducting a systematic review and meta-analysis. Methods: Studies that compared ERM vitrectomy with and without intraoperative dexamethasone implant with a follow-up ≥3 months were included. The primary outcome was mean best corrected visual acuity (BCVA) change between eyes undergoing ERM vitrectomy combined with dexamethasone implant (DEX group) and eyes undergoing ERM vitrectomy alone (control group) at 3 months. Secondary outcomes included mean BCVA change at 6 months and mean optical coherence tomography central macular thickness (CMT) change at both 3-months and 6-months follow-up. Mean differences (MDs) with their 95% confidence interval (95%CI) were calculated. Meta-analyses were based either on random effect model or fixed effect model according to heterogeneity. Results: Four studies were included. At 3 months, ERM vitrectomy combined with dexamethasone implant yielded a greater visual gain compared to vitrectomy alone (MD = 9.7; 95%CI = 2.6-16.8; p = 0.01). However, significant heterogeneity was found. A sensitivity analysis excluding the only retrospective non-randomized study confirmed a greater visual gain in the DEX group (MD = 7.1; 95%CI = 2.7-11.6; p < 0.01), with no heterogeneity. At 6 months, a non-significant but borderline difference in visual gain was shown between in the two groups (MD = 5.1; 95%CI = -0.3-10.5; p = 0.06), with no heterogeneity. Three-month analysis of CMT revealed a greater reduction in the DEX group (MD = -80.2; 95%CI =-149.1-11.2; p = 0.02), but with significant heterogeneity. A sensitivity analysis excluding the only retrospective non-randomized study allowed to reduce heterogeneity, but no difference in 3-months CMT change was found between the two groups (MD = -50.0; 95%CI = -106.2-6.2; p = 0.08). At 6 months, no difference in CMT change was shown between the two groups (MD = -48.5; 95%CI = -120.5-23.5; p = 0.19), with significant heterogeneity. Conclusions: Intraoperative dexamethasone implant in eyes undergoing vitrectomy for ERM provided a better visual outcome at 3 months compared to ERM vitrectomy without the implant, with limited evidence of better anatomic outcome as well. Further studies are needed to ascertain whether dexamethasone implant would ensure a significant long-term visual benefit as a result of a faster reduction of macular thickening.

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.

Primary vitrectomy for degenerative and tractional lamellar macular holes: A systematic review and meta-analysis.

PURPOSE: To assess the efficacy of vitrectomy in degenerative and tractional lamellar macular holes (LMHs) by meta-analysis of published studies. METHODS: PubMed, Medline and Embase databases were searched up to May 2020. Included cohorts were divided into three groups: degenerative LMH group, lamellar hole associated epiretinal proliferation (LHEP) group and tractional LMH group. LHEP is likely to be associated with degenerative LMHs, but less commonly could be associated with mixed LMHs. To reduce risk of possible misclassification bias, eyes with LHEP which could not have been precisely classified by the authors, were included into the LHEP group. The primary outcome was to investigate the visual change following primary vitrectomy in the degenerative LMH and LHEP group versus the tractional LMH group. A sensitivity analysis excluding the LHEP group was also performed on the primary outcome. Mean difference (MD) in best corrected visual acuity between baseline and post-treatment was calculated, along with 95% confidence interval (CI). Rate of incidence of post-operative full-thickness macular hole (FTMH) was assessed as secondary outcome. RESULTS: Thirteen studies were included. Pooled analyses including all groups showed a significant visual improvement following vitrectomy (pre-post MD = -0.17;95%CI = -0.22,-0.12;p<0.001), with no difference in visual improvement between the degenerative LMH and LHEP group and the tractional LMH group. The sensitivity analysis excluding LHEP group confirmed no difference in visual change between the degenerative LMH group (pre-post MD = -0.18;95%CI = -0.24,-0.12;p<0.001) and the tractional LMH group (MD = -0.16;95%CI = -0.26,-0.07;p<0.001). The incidence rate of post-operative FTMH was higher in the degenerative LMH and LHEP group than in the tractional LMH group (p = 0.002). CONCLUSION: Primary vitrectomy for LMH ensured a favorable visual outcome, with no difference in visual gain between degenerative and tractional LMHs. However, a higher incidence of post-operative FTMHs was found in eyes with the degenerative LMH subtype.

Fluocinolone acetonide vitreous insert for chronic diabetic macular oedema: a systematic review with meta-analysis of real-world experience.

We conducted a meta-analysis of real-world studies on the 0.19 mg Fluocinolone Acetonide (FAc) intravitreal implant for chronic diabetic macular oedema (DMO), comparing these findings with the Fluocinolone Acetonide for Diabetic Macular Edema (FAME) study. The primary outcome was mean change of best corrected visual acuity (BCVA) at 24 months. Secondary outcomes were 36-month mean BCVA, mean central macular thickness (CMT) change, rates of eyes receiving supplementary intravitreal therapy, cataract surgery, intraocular pressure (IOP)-lowering drops and glaucoma surgery. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Nine real-world studies were included. The FAc implant yielded a significantly improved BCVA at 24 and 36 months (24-month MD = 4.52; 95% CI 2.56-6.48; 36-month MD = 8.10; 95% CI 6.34-9.86). These findings were comparable with the FAME study. The FAc implant yielded significantly reduced 24- and 36-month CMT. Pooled proportions of cataract surgery, IOP-lowering drops and glaucoma surgery were 39%, 27% and 3%, respectively, all lower than the FAME study. Pooled estimate of supplementary intravitreal therapy was 39%, higher than the 15.2% of the FAME study. This meta-analysis of real-world studies confirms favorable visual and anatomical outcomes following FAc insert for chronic DMO. In real-life studies more than one third of patients received supplementary intravitreal therapy, an issue that needs to be further explored.

Factors predicting normal visual acuity following anatomically successful macular hole surgery.

PURPOSE: To assess the incidence of normal vision following anatomically successful macular hole surgery and associated clinical variables. METHODS: Multicentre, retrospective chart review. Preoperative, intraoperative and postoperative clinical data were extracted from electronic medical records from seven European vitreoretinal units. Inclusion criteria were as follows: eyes undergoing primary vitrectomy for idiopathic full-thickness macular hole from January 2015 to January 2018; postoperative macular hole closure confirmed by spectral domain optical coherence tomography (OCT); preoperative pseudophakia or phakic eyes receiving combined cataract surgery; one-year follow-up. The primary outcome was 'normal vision' defined as a final best-corrected visual acuity (BCVA) ≥ 20/25. Univariate, multivariate and decision-tree analyses were conducted to evaluate the clinical variables associated with 'normal vision'. Odds ratios (OR) and confidence intervals (CIs) were calculated. RESULTS: Of 327 eligible cases, 91 (27.8%) achieved 'normal vision' at 1 year. Multivariate analysis identified variables significantly associated with 'normal vision': shorter symptom duration (odds ratio [OR]=1.05; 95% confidence interval [CI]:1.02-1.09; p = 0.002), smaller preoperative OCT minimum linear diameter (OR per 100-micron increase = 1.65; 95%CI:1.31-2.08; p < 0.001) and better mean preoperative BCVA (OR = 15.13; 95%CI: 3.59-63.65; p < 0.001). The decision-tree analysis found that the most significant variable associated with 'normal vision' was symptom duration. 'Normal vision' was achieved in 70.6% of eyes operated within one week from symptom onset and in 45% of eyes with symptom duration between 1 and 3 weeks. CONCLUSIONS: These findings suggested urgent surgery is justified for small macular holes of short duration.

A Human Amniotic Membrane Plug to Treat Persistent Macular Hole.

The human amniotic membrane (hAM) has lately demonstrated interesting potential in its retinal applications. Nowadays, the treatment of persistent macular holes is still a challenge. In this paper, we present a case of a hAM plug used to treat a persistent macular hole, with the purpose of highlighting the critical issues of this new surgical procedure. We performed a 23-G pars plana vitrectomy and inserted a hAM plug (diameter of 1.5 mm) under the neuroretinal margins of the hole (diameter of 657 µm). A complete ophthalmic examination with the assessment of best-corrected visual acuity (logMAR units, ETDRS letter score) and optical coherence tomography (OCT) scans were collected at 1, 4, 6, and 10 weeks after surgery. Visual acuity changed from logMAR 1.0 (1) preoperatively to logMAR 1.0 (2), 1.0 (4), 0.9 (9), and 0.9 (10) at 1, 4, 6, and 10 weeks of follow-up, respectively. The 1 week postoperative OCT did not show neuroretinal adhesion over the plug, but the following visits showed reattachment of the margins with partial neuroretinal ingrowth. These findings suggest that the correct adaptation of the size of the hAM plug to the macular hole is essential to allow the anatomical closure of the hole and potential functional results.

Hypertensive emergencies and urgencies in emergency departments: a systematic review and meta-analysis.

OBJECTIVES: The prevalence of hypertensive emergencies and urgencies and of acute hypertension-mediated organ damage (aHMOD) in emergency departments is unknown. Moreover, the predictive value of symptoms, blood pressure (BP) levels and cardiovascular risk factors to suspect the presence of aHMOD is still unclear. The aim of this study was to investigate the prevalence of hypertensive emergencies and hypertensive urgencies in emergency departments and of the relative frequency of subtypes of aHMOD, as well as to assess the clinical variables associated with aHMOD. METHODS: We conducted a systematic literature search on PubMed, OVID, and Web of Science from their inception to 22 August 2019. Two independent investigators extracted study-level data for a random-effects meta-analysis. RESULTS: Eight studies were analysed, including 1970 hypertensive emergencies and 4983 hypertensive urgencies. The prevalence of hypertensive emergencies and hypertensive urgencies was 0.3 and 0.9%, respectively [odds ratio for hypertensive urgencies vs. hypertensive emergencies 2.5 (1.4-4.3)]. Pulmonary oedema/heart failure was the most frequent subtype of aHMOD (32%), followed by ischemic stroke (29%), acute coronary syndrome (18%), haemorrhagic stroke (11%), acute aortic syndrome (2%) and hypertensive encephalopathy (2%). No clinically meaningful difference was found for BP levels at presentations. Hypertensive urgency patients were younger than hypertensive emergency patients by 5.4 years and more often complained of nonspecific symptoms and/or headache, whereas specific symptoms were more frequent among hypertensive emergency patients. CONCLUSION: Hypertensive emergencies and hypertensive urgencies are a frequent cause of access to emergency departments, with hypertensive urgencies being significantly more common. BP levels alone do not reliably predict the presence of aHMOD, which should be suspected according to the presenting signs and symptoms.

Anti-inflammatory Effect of Curcumin, Homotaurine, and Vitamin D3 on Human Vitreous in Patients With Diabetic Retinopathy.

Purpose: To determine the levels of pro-inflammatory cytokines and soluble mediators (TNF-α, IL6, IL2, and PDGF-AB) in 28 vitreous biopsies taken from patients with proliferative diabetic retinopathy (PDR) and treated with increasing doses of curcumin (0. 5 and 1 µM), with or without homotaurine (100 µM) and vitamin D3 (50 nM). Materials and Methods: ELISA tests were performed on the supernatants from 28 vitreous biopsies that were incubated with bioactive molecules at 37°C for 20 h. The concentration of the soluble mediators was calculated from a calibration curve and expressed in pg/mL. Shapiro-Wilk test was used to verify the normality of distribution of the residuals. Continuous variables among groups were compared using the General Linear Model (GLM). Homoscedasticity was verified using Levene and Brown-Forsythe tests. Post-hoc analysis was also performed with the Tukey test. A p ≤ 0.05 was considered statistically significant. Results: The post-hoc analysis revealed statistically detectable changes in the concentrations of TNF-α, IL2, and PDGF-AB in response to the treatment with curcumin, homotaurine, and vitamin D3. Specifically, the p-values for between group comparisons are as follows: TNF-α: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.008, (curcumin 0.5 µM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0004, (curcumin 0.5 µM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.02, (curcumin 1 µM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.025, and (homotaurine 100 µM + vitamin D3 50 nM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.009; IL2: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0023, and (curcumin 0.5 µM vs. curcumin 0.5 µM+ homotaurine 100 µM + vitamin D3 50 nM) p = 0.0028; PDGF-AB: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.04, (untreated vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0006, (curcumin 0.5 µM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.006, and (homotaurine 100 µM + vitamin D3 50 nM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.022. IL6 levels were not significantly affected by any treatment. Conclusions: Pro-inflammatory cytokines are associated with inflammation and angiogenesis, although there is a discrete variability in the doses of the mediators investigated among the different vitreous samples. Curcumin, homotaurine, and vitamin D3 individually have a slightly appreciable anti-inflammatory effect. However, when used in combination, these substances are able to modify the average levels of the soluble mediators of inflammation and retinal damage. Multi-target treatment may provide a therapeutic strategy for diabetic retinopathy in the future. Clinical Trial Registration : The trial was registered at clinical trials.gov as NCT04378972 on 06 May 2020 ("retrospectively registered") https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid = S0009UI8&selectaction = Edit&uid = U0003RKC&ts = 2&cx = dstm4o.

The foveal photoreceptor layer and visual acuity loss in central serous chorioretinopathy.

PURPOSE: To describe changes of the foveal photoreceptor layer using optical coherence tomography (OCT) in central serous chorioretinopathy (CSC) and evaluate the correlation with visual acuity (VA) loss. DESIGN: Observational case series. METHODS: We studied 28 eyes with acute or chronic CSC using high-resolution OCT. The tomographic findings of the detached foveal photoreceptor layer were compared with VA. Sixteen eyes also were evaluated after foveal reattachment. RESULTS: The outer photoreceptor layer (OPL) in the detached fovea was preserved in 14 eyes, of which 13 had symptoms for <1 year and atrophic in 14 eyes with symptoms for >1 year. The preserved OPL had an even profile in 7 eyes and a granulated profile in 7 eyes. Mean VA was 0.19 logMAR with a preserved OPL and 0.72 logMAR with an atrophic OPL (P <.001). Cases seen after the detachment resolved included 6 eyes with preserved even OPL, 5 eyes with preserved granulated OPL, and 5 eyes with atrophic OPL. Mean final VA was 0.06 logMAR in eyes with preserved OPL and 0.90 logMAR in eyes with atrophic OPL (P <.001). The VA improved in 73% of eyes with preserved OPL and no eyes with atrophic OPL (P = .025). The VA recovered completely in 83% of eyes with preserved even OPL and no eyes with preserved granulated OPL (P = .015). CONCLUSION: High-resolution OCT demonstrates changes in the foveal photoreceptor layer in CSC that highly correlate with VA loss and may predict visual recovery after macular reattachment.

Photodynamic therapy for chronic central serous chorioretinopathy.

PURPOSE: To determine whether photodynamic therapy (PDT) is effective for treatment of chronic central serous chorioretinopathy (CSC). METHODS: Sixteen eyes with chronic CSC and macular detachment documented by optical coherence tomography (OCT) received PDT guided by indocyanine green (ICG) angiography according to the parameters outlined in the TAP Study. One or more laser spots were applied to the areas of choroidal vascular hyperpermeability that corresponded to retinal pigment epithelium decompensation. Patients were observed for 6 to 12 months. Two PDT sessions 1 month apart were performed on 2 eyes. Examinations included visual acuity measurement, fundus biomicroscopy, fluorescein and ICG angiography, and OCT. RESULTS: Macular exudation resolved completely in 13 eyes (81%) and partially regressed in 3. Choriocapillaris hypoperfusion was shown by ICG angiography for several months at the site of PDT application. Visual acuity improved 1 to 4 lines in 11 eyes and was unchanged in 5 eyes. CONCLUSIONS: ICG-guided PDT performed according to the parameters outlined by the TAP Study seems effective for treating chronic CSC. Further studies are needed to verify treatment safety and the time and rate of recurrences.