The effect of pars plana vitrectomy with internal limiting membrane peeling on the durability of the intravitreal dexamethasone implant in the treatment of diabetic macular edema

Purpose: To evaluate the influence of pars plana vitrectomy with internal limiting membrane peeling on recurrence time of diabetic macular edema in eyes under treatment with dexamethasone intravitreal implant injections. Material and methods: Twelve pseudophakic eyes of 12 patients with non-proliferative diabetic retinopathy and non-tractional diabetic macular edema were included. All eyes had already been treated with two or more dexamethasone intravitreal implant injections evidencing a recurrence time of three months or less (early recurrence). At baseline, they underwent pars plana vitrectomy with internal limiting membrane peeling, ending with dexamethasone intravitreal implant injection. Patients were then followed-up monthly, treated with a second injection at the first recurrence, and followed up to the second recurrence. Measurements of best corrected visual acuity, intraocular pressure, and central foveal thickness by spectral-domain optical coherence tomography were performed at each follow-up examination. Results: Vitrectomized eyes showed a significant extension of recurrence time of diabetic macular edema, and specifically from 3.4 (3.2-3.7) to 6.5 (5.7-8.2) months after the first injection, and to 7.0 (5.7-8.2) months (p < 0.01) after the second injection (p < 0.01). Conclusions and importance: Pars plana vitrectomy with internal limiting membrane peeling seems not to influence functional and anatomical results in eyes under treatment with dexamethasone intravitreal implant injections for diabetic macular edema, but appears to significantly extend the benefit of the drug

Morphologic Criteria of Lesion Activity in Neovascular Age-Related Macular Degeneration: A Consensus Article

Intravitreal antivascular endothelial growth factor drugs represent the current standard of care for neovascular age-related macular degeneration (nAMD). Individualized treatment regimens aim at obtaining the same visual benefits of monthly injections with a reduced number of injections and follow-up visits, and, consequently, of treatment burden. The target of these strategies is to timely recognize lesion recurrence, even before visual deterioration. Early detection of lesion activity is critical to ensure that clinical outcomes are not compromised by inappropriate delays in treatment, but questions remain on how to effectively monitor the choroidal neovascularization (CNV) activity. To assess the persistence/recurrence of lesion activity in patients undergoing treatment for nAMD, an expert panel developed a decision algorithm based on the morphological features of CNV. After evaluating all current retinal imaging techniques, the panel identified optical coherent tomography as the most reliable tool to ascertain lesion activity when funduscopy is not obvious

An optical coherence tomography-based grading of diabetic maculopathy proposed by an international expert panel: The European School for Advanced Studies in Ophthalmology classification.

Aims:To present an authoritative, universal, easy-to-use morphologic classification of diabetic maculopathy based on spectral domain optical coherence tomography.Methods:The first draft of the project was developed based on previously published classifications and a literature search regarding the spectral domain optical coherence tomography quantitative and qualitative features of diabetic maculopathy. This draft was sent to an international panel of retina experts for a first revision. The panel met at the European School for Advanced Studies in Ophthalmology headquarters in Lugano, Switzerland, and elaborated the final document.Results:Seven tomographic qualitative and quantitative features are taken into account and scored according to a grading protocol termed TCED-HFV, which includes foveal thickness (T), corresponding to either central subfoveal thickness or macular volume, intraretinal cysts (C), the ellipsoid zone (EZ) and/or external limiting membrane (ELM) status (E), presence of disorganization of the inner retinal layers (D), number of hyperreflective foci (H), subfoveal fluid (F), and vitreoretinal relationship (V). Four different stages of the disease, that is, early diabetic maculopathy, advanced diabetic maculopathy, severe diabetic maculopathy, and atrophic maculopathy, are based on the first four variables, namely the T, C, E, and D. The different stages reflect progressive severity of the disease.Conclusion:A novel grading system of diabetic maculopathy is hereby proposed. The classification is aimed at providing a simple, direct, objective tool to classify diabetic maculopathy (irrespective to the treatment status) even for non-retinal experts and can be used for therapeutic and prognostic purposes, as well as for correct evaluation and reproducibility of clinical investigations

Dexamethasone intravitreal implant for diabetic macular edema: indications for a PRN regimen of treatment

Purpose: To define the mean time of first recurrence of diabetic macular edema (DME) after a single injection of dexamethasone intravitreal implant (DEX-I), reducing the burden of monthly visits during a PRN regimen of treatment. Methods: Twenty phakic eyes with DME (12 eyes naïve and 8 eyes with edema persistent after previous treatments) were followed monthly after DEX-I injection until evidence of first recurrence of edema, defined as a change in visual acuity (VA) ≥5 letters and/or in foveal thickness (FT) ≥50 μm. Reaching this point, the eyes were re-treated. Monitored parameters were changes in VA, FT, intraocular pressure (IOP), and lens opacity. Results: Maximal efficacy was registered at month 1, when mean VA improved by 14 letters (19%), FT decreased by 325 μm (43.7%), and in 15 eyes (75%) edema was completely reabsorbed. The mean time of first recurrence was 5.1 months. No statistical difference was found between eyes with naïve or persistent DME. Five eyes needed topical medication for modest temporary IOP increase (21-24 mm Hg) between months 2 and 4. No increase in lens opacities was registered during follow-up. Conclusions: According to the results of this study, the first signs of DME recurrence after DEX-I injection appear at a mean time of 5 months, suggesting that an appropriate and prudent time schedule for a PRN regimen could be limited to monthly tonometry and a first complete examination not before 4 months

Dexamethasone intravitreal implant at the time of cataract surgery in eyes with diabetic macular edema

Purpose: To determine the potential role of intraoperative dexamethasone intravitreal implant (DEX-I) in reducing diabetic macular edema (DME) worsening after phacoemulsification.Methods: This was a prospective study on 19 eyes of 19 patients with type 2 diabetes mellitus with DME and cataract. Mean preoperative Early Treatment Diabetic Retinopathy Study visual acuity (VA) was 16.7 letters. Mean foveal thickness (FT) was 451 mu m. The DME was naive in 11 eyes and refractory in 8 eyes. All eyes underwent a standard phacoemulsification and intraocular lens implantation; DEX-I was injected at the end of surgery. Followup was performed at 1 week and then monthly until DME recurrence (up to 8 months).Results: At 1 week, mean VA improved by 15 letters (range 0-29 letters) and mean FT decreased by 147 mu m (range 69-236 mu m). Improvement consolidated at month 1, with a mean VA improvement of 18 letters (range 3-32 letters) and a mean improvement in FT of 193 mu m (range 76-304 mu m), remaining stable at month 2 after surgery in all eyes. The DME recurred in 1 eye at month 3, in 14 eyes (73.8%) between months 4 and 5, and after month 6 in 4 eyes (21%). Refractory DMEs demonstrated the same benefit but recurred earlier than naive ones (4 months versus 5.8 months, p<0.01).Conclusions: Intraoperative DEX-I prevents DME worsening after phacoemulsification. Its positive effects last for at least 3 months

Novel artificial tears containing cross-linked hyaluronic acid: An in vitro re-epithelialization study

Dry eye syndrome is a common disease which can damage the corneal epithelium. It is treated with eye drops to stimulate tear production and hydrate the corneal surface. The most prescribed artificial tear remedies contain hyaluronic acid (HA), which enhances epithelial wound healing, improving tissue health. To the best of our knowledge, only a few recent studies have investigated cross-linked HA (HA-CL) in eye drops for human applications. This work consists in an in vitro evaluation of the re-epithelialization ability of two different preparations containing a recently synthetized HA cross-linked with urea: 0.02% (w/v) HA-CL (solution 1, S1), and 0.4% (w/v) HA-CL (solution 2, S2). The study was conducted on both 2D human corneal cells (HCEpiC) and 3D reconstructed tissues of human corneal epithelium (HCE). Viability by 3(4,5-dimethylthiazol-2)2,5-diphenyltetrazolium bromide (MTT) test, pro-inflammatory cytokine release (interleukin-8, IL-8) by ELISA, and morphology by hematoxylin and eosin (HE) staining were evaluated. In addition, to understand the molecular basis of the re-epithelialization properties, cyclin D1 levels were assessed by western blot. The results showed no cellular toxicity, a slight decrease in IL-8 release, and restoration of epithelium integrity when the wounded 3D model was treated with S1 and S2. In parallel, cyclin D1 levels increased in cells treated with both S1 and S2

Role of OCT in the diagnosis and follow up of diabetic macular edema

The aim is to present, along with a brief literature review, the results of OCT scan in eyes with diabetic macular edema (DME), as well as examples of the utility of OCT for different therapeutic approaches. One-hundred and thirty-six eyes with diabetic retinopathy were analyzed with OCT to explore the different patterns of DME. Some eyes with DME were studied with OCT pre and postoperatively to determine the efficacy of photocoagulation and vitrectomy to restore a normal macular profile. Sixty-eight eyes with a central foveal thickness of 200 mu or more were considered "edematous". Three different patterns of DME were recognized and analyzed: macular thickening, cystoid macular edema and shallow retinal detachment. The change in macular profile and internal retinal structure after laser or surgical treatment are well visible with OCT. OCT contributes in understanding the anatomy of DME and the intraretinal damage and seems to be the technique of choice for the follow-up of macular edema. We think that this tool should always be used in monitoring the effect of therapies in future studies

Clinical improvement of ocular surface parameters in dry eye patients following treatment with urea/crosslinked-hyaluronate eyedrops correlates with the secretion of MUC-4

Objectives: To assess the ocular surface status after treatment with urea/crosslinked hyaluronate (U-HACL) tear substitute in dry eye (DE) patients. Methods: Seventeen DE patients were included in the study. They instilled U-HACL drops three times/day for 2 months. Symptoms (by OSDI and VAS), osmolarity, tear film (through Schirmer and tear film breakup time), corneal and conjunctival damage (with NEI and van Bijsterveld scores), impression cytology (number of PAS positive cells and MUC-4 immunostaining), and tear sampling were analyzed pre- and posttreatment. Results: After the treatment, there was a significant improvement of VAS (7.16 ± 2.59 vs. 3.94 ± 2.23), OSDI (56.96 ± 25.97 vs. 29.94 ± 20.15), Schirmer (8.22 ± 6.86 vs. 10.66 ± 6.92), TFBUT (3.16 ± 2.28 vs. 5.55 ± 2.47), NEI (7.16 ± 2.50 vs. 2.88 ± 2.80), and van Bijsterveld (10.27 ± 4.25 vs. 6.5 ± 3.79) score, p < 0.01. There was a significant increase of PAS positive cells and MUC-4 (respectively, 44.21 ± 14.8 vs. 67.0 ± 10.1 and 49.79 ± 20.0 vs. 75.9 ± 20.7), p < 0.01. Conclusion: The rise of MUC-4 expression probably contributed to the increase in ocular wettability and amelioration of clinical parameters following the administration of U-HACL eye drops

Validation of Esaso Classification of Diabetic Maculopathy

Purpose: To test reliability and reproducibility of ESASO morphologic OCT-based classification of diabetic maculopathy (DM). Methods: This is a multi-center cross-sectional study including a coordination center (CC) and 18 participating centers (PCs). After instruction on the correct use of ESASO Classification, the validation process was carried out in two consecutive stages. In the first retrospective phase, we evaluated the concordance between PCs and CC in the staging of OCT images collected during PCs' daily activity (608 images). In a second prospective phase, we analyzed the inter-observer agreement of staging assigned by each PCs to OCT images selected by the CC (22 images). Results: The overall concordance achieved in the retrospective phase was 89.8% (Kappa = 0.83 (95% CI: 0.78-0.87); p<0.0001). In 99.5% of cases, concordance did not differ by more than one stage. In the prospective phase, PCs reached an inter-operator agreement of 93.0% (Krippendorff's Alpha = 0.953, 95% CI: 0.929-0.977, p<0.0001). Any discrepancy among the 22 images was within one stage. Conclusion: The results achieved in this study confirm that ESASO OCT-based Classification can be considered as an easy and reproducible method to stage DM during clinical practice. A diffused use of a common and validated method to describe the progression of retinal damage in DM may offer several clinical and scientific advantages