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BACKGROUND AND OBJECTIVE: To compare capillary density (CD) changes assessed by optical coherence tomography angiography (OCTA) during diabetic retinopathy (DR) progression using three previously published methods: binarization, skeletonization, and automated flow density (AFD). PATIENTS AND METHODS: Retrospective study of 98 eyes of 74 patients with diabetes and 18 control eyes imaged using OCTA. The macular CD at each stage of DR was assessed using the three methods and were compared to control eyes. RESULTS: AFD was the only method that detected differences between controls and severe nonproliferative DR eyes. The three methods showed a significant difference in CD between controls and eyes with proliferative DR, except for the “fovea” area. CONCLUSION: Only one of the three methods allowed for the detection of changes from the normal capillary density as early as at the “severe nonproliferative DR” stage due to several refinements from the basic technique. [ Ophthalmic Surg Lasers Imaging Retina. 2017;48:378–384.]

To compare characteristics of functioning blebs (FBs) and nonfunctioning blebs (NFBs) with en-face spectral-domain optical coherence tomography (OCT).We evaluated 41 blebs of 38 patients after a first-time trabeculectomy. Eyes were classified into 2 groups: FBs (22 eyes) and NFBs (19 eyes). En-face OCT images were analyzed semiquantitatively for the density of intraepithelial microcysts (0 to 3), internal fluid-filled cavity (0 to 3), and bleb vascularization (0 to 2). Presence of conjunctival fibrosis and visualization of the scleral flap were also analyzed.FBs showed significantly more intraepithelial microcysts than did NFBs: the mean grading of microcyst density was 1.86 for FBs and 0.11 for NFBs (P0.0001). None of the FBs were rated 0 and none of the NFBs were rated 2 or 3 for the density of intraepithelial microcysts. NFBs presented more conjunctival fibrosis than FBs (63% vs. 32%, P0.05). There was no significant difference between FBs and NFBs for bleb vascularization, visualization of the scleral flap, and presence of subepithelial fluid-filled cavities. There was a direct correlation between postoperative intraocular pressure and intraepithelial microcyst density (r=-0.7655, P0.0001). The long-term administration of preserved eyedrops before surgery was associated with fewer intraepithelial microcysts (r=-0.5436; P=0.0006).FBs were associated with a higher number of intraepithelial microcysts evaluated with en-face OCT. A higher density of microcysts was associated with a lower intraocular pressure and a shorter duration of preserved topical treatment before surgery. En-face OCT provides a simple, noninvasive, and reproducible method to analyze blebs after filtering surgery.

Purpose To study the symmetry in response to bilateral diabetic macular oedema (DME) treated with bilateral intravitreal injections of ranibizumab (IVR). Methods The charts of 36 eyes of 18 patients treated with a loading dose of three monthly IVR in both eyes were retrospectively reviewed. Favourable anatomical response was defined as a decrease by more than 10% in baseline central macular thickness (CMT), and favourable functional response was defined as an increase in visual acuity (VA) ≥5 letters. A symmetric response was defined as a similar anatomical and/or functional response in the first (FE) and second (SE) treated eyes. Results The VA improved significantly after ranibizumab treatment in both eyes (p

Background To evaluate the incidence, evolution, clinical characteristics, possible risk factors or preventive factors, and visual outcomes of epiretinal membrane (ERM) recurrence. Methods Retrospective study of 440 consecutive patients (440 eyes) who underwent pars plana vitrectomy for ERM. The internal limiting membrane (ILM) was peeled in 266 cases, with the help of indocyanine green in 27 cases and brilliant blue in 45 cases. Cases of symptomatic ERM recurrence were reoperated. Results The incidence of ERM recurrence was 5% (22/440), and 2% of the patients were reoperated (9/440). Epiretinal membrane recurrence was symptomatic in 9 cases (41%) and asymptomatic in 13 cases (59%). ILM peeling was the only factor preventing ERM recurrence (adjusted odds ratio = 0.33, P = 0.026). The use of staining dyes did not prevent recurrence (adjusted odds ratio = 0.35, P = 0.338). In the case of ERM reproliferation, the absence of ILM peeling, the existence of ERM on the fellow eye, and poor visual acuity before surgery seemed to be associated with a high risk of symptomatic recurrence and reoperation. The mean duration for follow-up was 3.5 ± 1.7 years. Conclusion ILM peeling not only reduces the likelihood of reproliferation of ERM but also seems to improve the visual prognosis of recurrent ERMs. The use of dyes did not reduce the rate of recurrence compared with when ILM was peeled without dyes.

Photoreceptors and retinal pigment epithelial cells (RPE) targeting remains challenging in ocular gene therapy. Viral gene transfer, the only method having reached clinical evaluation, still raises safety concerns when administered via subretinal injections. We have developed a novel transfection method in the adult rat, called suprachoroidal electrotransfer (ET), combining the administration of nonviral plasmid DNA into the suprachoroidal space with the application of an electrical field. Optimization of injection, electrical parameters and external electrodes geometry using a reporter plasmid, resulted in a large area of transfected tissues. Not only choroidal cells but also RPE, and potentially photoreceptors, were efficiently transduced for at least a month when using a cytomegalovirus (CMV) promoter. No ocular complications were recorded by angiographic, electroretinographic, and histological analyses, demonstrating that under selected conditions the procedure is devoid of side effects on the retina or the vasculature integrity. Moreover, a significant inhibition of laser induced-choroidal neovascularization (CNV) was achieved 15 days after transfection of a soluble vascular endothelial growth factor receptor-1 (sFlt-1)-encoding plasmid. This is the first nonviral gene transfer technique that is efficient for RPE targeting without inducing retinal detachment. This novel minimally invasive nonviral gene therapy method may open new prospects for human retinal therapies.

This study aimed to assess application of ultrasound (US) combined with microbubbles (MB) to transfect the ciliary muscle of rat eyes. Reporter DNA plasmids encoding for Gaussia luciferase , β-galactosidase or the green fluorescent protein (GFP), alone or mixed with 50% Artison MB, were injected into the ciliary muscle, with or without US exposure (US set at 1 MHz, 2 W/cm 2 , 50% duty cycle for 2 min). Luciferase activity was measured in ocular fluids at 7 and 30 days after sonoporation. At 1 week, the US+MB treatment showed a significant increase in luminescence compared with control eyes, injected with plasmid only, with or without MB (×2.6), and, reporter proteins were localized in the ciliary muscle by histochemical analysis. At 1 month, a significant decrease in luciferase activity was observed in all groups. A rise in lens and ciliary muscle temperature was measured during the procedure but did not result in any observable or microscopic damages at 1 and 8 days. The feasibility to transfer gene into the ciliary muscle by US and MB suggests that sonoporation may allow intraocular production of proteins for the treatment of inflammatory, angiogenic and/or degenerative retinal diseases.

To compare the safety and functional outcomes of 25-gauge and 23-gauge (G) micro-incision vitrectomy surgery (MIVS) instrumentation with the standard 20-G vitrectomy system in the treatment of epiretinal membranes (ERM). A retrospective comparative study of 553 consecutive cases with epiretinal membrane who underwent pars plana vitrectomy. Twenty-gauge, 25-gauge and 23-gauge vitrectomy was performed respectively in 347, 91, and 115 eyes. Surgery duration, visual acuity improvement, intraocular pressure variation, intraoperative and postoperative complications were analyzed. The mean surgical time in the 23-G group and in the 25-G group was shorter than in the 20-G group (P

To define the optical coherence tomography (OCT) corneal changes predisposing to acute corneal hydrops among patients with advanced keratoconus.Retrospective cohort study.A total of 191 advanced keratoconic eyes from 191 patients with advanced keratoconus cases were studied.Data collected from patients with advanced keratoconus cases were studied during a minimum period of 24 months of follow-up. High-resolution Fourier-domain corneal OCT (5 μm of axial resolution) and corneal topography were performed every 4 months during the follow-up. Several anatomic features at the keratoconus cone were analyzed with OCT, including epithelial and stromal thicknesses, the aspect of Bowman's layer, the presence of Vogt's striae, and stromal opacities. A comparative analysis between anatomic corneal features in eyes that developed corneal hydrops and those that did not develop this complication during the follow-up was performed.Evaluation of anatomic corneal changes at risk of developing a corneal hydrops on the basis of OCT findings.Eleven cases of corneal hydrops (5.8%) occurred in our series during a mean follow-up of 30 months (24-36 months). All of these patients were male and younger (23.7±5.9 years) than patients with no acute keratoconus (32.7±11.3 years). Increased epithelial thickening with stromal thinning at the conus and the presence of anterior hyperreflectives at the Bowman's layer level were significantly associated with corneal hydrops, whereas the presence of corneal scarring was a preventive factor. At the healing stage, a pan-stromal scar occurs, with a significant stromal thickening and cornea flattening.Increased epithelial thickening, stromal thinning at the keratoconus cone, anterior hyperreflectives at the Bowman's layer level, and the absence of stromal scarring are associated with a high risk of developing corneal hydrops. These aspects should be taken into account by the clinician in the evaluation of keratoconus eyes and in the planning of corneal keratoplasty.

Purpose To assess the efficacy of a single dexamethasone intravitreal implant (Dex-I) injection for the treatment of diabetic macular edema (DME). Methods This was a retrospective chart review of 39 eyes (34 consecutive patients). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and increase in intraocular pressure (IOP) (>24 mm Hg) were analyzed before treatment and 2 and 4 months after injection. Results Preoperative mean CMT was 559 ± 111 μm and decreased to 338 ± 84 and 477 ± 140 μm 2 and 4 months after injection, respectively. Although all eyes showed a significant decrease in CMT 2 months after injection (pConclusions Thirty percent of DME eyes had gained more than 2 logMAR lines 2 months after Dex-I injection and safety was good. Visual acuity gain was maintained 4 months after injection despite a recurrence of edema in most cases.

Purpose To evaluate a possible clinical application of spectral-domain optical coherence tomography (SD-OCT) using en-face module for the imaging of the corneoscleral limbus in normal subjects and dry eye patients. Patients and methods Seventy-six subjects were included in this study. Seventy eyes of 35 consecutive patients with dry eye disease and 82 eyes of 41 healthy control subjects were investigated. All subjects were examined with the Avanti RTVue® anterior segment OCT. En-face OCT images of the corneoscleral limbus were acquired in four quadrants (inferior, superior, nasal and temporal) and then were analyzed semi-quantitatively according to whether or not palisades of Vogt (POV) were visible. En-face OCT images were then compared to in vivo confocal microscopy (IVCM) in eleven eyes of 7 healthy and dry eye patients. Results En-face SD-OCT showed POV as a radially oriented network, located in superficial corneoscleral limbus, with a good correlation with IVCM features. It provided an easy and reproducible identification of POV without any special preparation or any direct contact, with a grading scale from 0 (no visualization) to 3 (high visualization). The POV were found predominantly in superior (P

To compare the long-term outcomes of vitreomacular surgery in eyes with nontractional diabetic macular edema (DME) with those from eyes with tractional DME.Retrospective comparative study from 55 consecutive patients (73 eyes). Twenty eyes were operated on for tractional DME and 53 eyes for nontractional DME unresponsive to laser photocoagulation or triamcinolone intravitreal injections. The best-corrected visual acuity, the central macular thickness, and the surgical complications were analyzed.The mean follow-up duration was 5.3 ± 2.4 years for the group with traction and 4.4 ± 1.7 years for the group without traction (P = 0.13). At 3 years, the mean logarithm of the minimum angle of resolution best-corrected visual acuity had improved significantly from 0.78 to 0.58 for the group without traction and from 0.75 to 0.45 for the group with traction (P0.001). At the final visit, there was no significant difference between the 2 groups in regard to visual or central macular thickness improvement (P = 0.447 and P = 0.742, respectively). The incidence of surgical complications was not significant between the two groups. The preoperative best-corrected visual acuity was the only predictive factor for the final best-corrected visual acuity.The results of vitrectomy were not different in terms of anatomical and visual outcomes and surgical complications between eyes without tractional DME and eyes with tractional DME.

The aim of this study was to describe a novel technique combining deep intrastromal arcuate keratotomy and superficial lamellar keratotomy followed by excimer photoablation for the management of high naturally occurring or postkeratoplasty astigmatism.In this retrospective case series, the first step was deep intrastromal arcuate keratotomy and superficial lamellar keratotomy performed at 100-μm depth by femtosecond laser. Manual incisions were made for flap elevation. The second step, after 1 month, consisted of reopening the flap and using an excimer laser to correct residual ametropia.Nine eyes series were studied. The mean preoperative refractive cylinder correction was 6.11 ± 2.54 diopters (D). The mean postoperative refractive cylinder correction was 2.85 ± 1.31 D. The mean correction index was 1.07 ± 0.28 D. The mean best-corrected visual acuity improved from 20/40 to 20/22 after the 2 steps. The median follow-up was 11 (range, 9-17) months. No complications were observed and postoperative outcome was satisfactory.Permitting correction of a broader range of high astigmatism with good accuracy, this combined approach minimizes excision of corneal stromal tissue and postoperative complications.

Purpose To explore the potential of spectral-domain optical coherence tomography (SD-OCT) using the en-face technology for the imaging of ocular surface diseases and to correlate the findings with in vivo confocal microscopy (IVCM) images. Patients and methods 113 eyes of 75 subjects with various ocular surface diseases were investigated with the RTVue ® anterior-segment en face OCT. En face OCT images were compared to B-scan OCT and IVCM images. Results Patients with corneal dystrophies, corneal deposits, keratitis, pterygium, conjunctivochalasis, or ocular surface squamous neoplasia and patients who underwent lamellar corneal surgeries were included. En-face OCT images showed ocular surface tissue changes that were not discernible using conventional B-scan OCT. Nevertheless, there was a good correlation with IVCM analysis. Compared with IVCM, the major advantages of en-face OCT included easy operation and rapid image acquisition, with minimal operator experience required. In addition, the non-contact method avoided patient discomfort and external pressure on the globe, which was especially useful in patients with corneal dystrophies, ulcers, or corneal abscesses. Although the resolution of en-face OCT was lower than that of IVCM, it allowed useful overall visualization of corneal lesions due to the larger areas analyzed. Conclusion En-face SD-OCT is a novel, valuable tool to assess a wide variety of ocular surface diseases. It can provide additional information and new insight into different ocular surface conditions with no corneal contact.

To determine whether optical coherence tomography (OCT) epithelial mapping can improve the detection of form fruste keratoconus.French National Eye Hospital, Paris 6 PierreMarie Curie University, Paris, France.Retrospective comparative study.Eyes with normal corneas, form fruste keratoconus, moderate keratoconus, or severe keratoconus were assessed using Fourier-domain OCT (RTVue 5.5), scanning-slit corneal topography (Orbscan IIz), and rotating Scheimpflug camera (Pentacam Comprehensive Eye Scanner). Several parameters provided by the software or derived from elevation maps, OCT pachymetric maps, and OCT epithelium parameters were evaluated and compared between the 4 groups.The study involved 145 eyes. There were no significant differences in the keratometry (K) value, inferior-superior value, keratoconus index, central K index, and topographic keratoconus classification indices between the form fruste keratoconus group and the control group (P .05). Form fruste keratoconic corneas had less epithelial thickness in the thinnest corneal zone than normal corneas, and greater epithelial thickness in the thinnest corneal zone than keratoconic corneas (P .005). The epithelial thickness in the thinnest corneal zone in form fruste corneas was located inferiorly (P .005) and corresponded with the zone of minimum epithelial thickness and maximum posterior elevation (P .005). The receiver operating characteristic curve analysis showed good overall predictive accuracy of the epithelial thickness in the thinnest corneal zone, with a 52 μm threshold value for discriminating form fruste keratoconic corneas from normal corneas.The epithelial thickness in the thinnest corneal zone and its location provided by the OCT epithelial mapping might be useful for the early diagnosis of form fruste keratoconus.No author has a financial or proprietary interest in any material or method mentioned.

To study corneal morphologic changes in a large keratoconic population and to establish a structural optical coherence tomography (OCT) classification.Cross-sectional, observational study.A total of 218 keratoconic eyes from 218 patients and 34 eyes from 34 normal subjects.A Fourier-domain OCT system with 5-μm axial resolution was used. For each patient, 3 high-resolution scans were made across the keratoconus cone. All scans were analyzed by keratoconus specialists who were not given access to patients' clinical and topographic data, and who established an OCT classification. The reproducibility of the classification and its correlation with clinical and paraclinical characteristics of patients with keratoconus were evaluated. The OCT examinations were performed every 4 months to follow up structural corneal changes.Evaluation of the structural corneal changes occurring in keratoconus cases with various stages of severity based on OCT findings.Fourier-domain OCT classification containing 5 distinct keratoconus stages is proposed. Stage 1 demonstrates thinning of apparently normal epithelial and stromal layers at the conus. Stage 2 demonstrates hyperreflective anomalies occurring at the Bowman's layer level with epithelial thickening at the conus. Stage 3 demonstrates posterior displacement of the hyperreflective structures occurring at the Bowman's layer level with increased epithelial thickening and stromal thinning. Stage 4 demonstrates pan-stromal scar. Stage 5 demonstrates hydrops; 5a, acute onset: Descemet's membrane rupture and dilaceration of collagen lamellae with large fluid-filled intrastromal cysts; 5b, healing stage: pan-stromal scarring with a remaining aspect of Descemet's membrane rupture. The reproducibility of the classification was very high between the corneal specialist observers. Clinical and paraclinical characteristics of keratoconus, including visual acuity, corneal epithelium and stromal thickness changes, corneal topography, biomechanical corneal characteristics, and microstructural changes observed on confocal microscopy, were concordant with our OCT grading.Optical coherence tomography provides an accurate assessment of structural changes occurring in keratoconus eyes. These changes were correlated with clinical and paraclinical characteristics of patients. The established classification not only allows structural follow-up of patients with keratoconus but also provides insight into the pathogenesis of keratoconus and treatment strategies for future research.

To compare the 23-gauge (23-G) sutureless vitrectomy incision architecture in macular and non-macular surgery, using anterior segment spectral-domain optical coherence tomography (SD-OCT), and to evaluated its influence on clinical outcomes.A prospective, observational case series of 43 patients who underwent primary transconjunctival 23-G pars plana vitrectomy (PPV) for macular and non-macular diseases. All sclerotomy wounds were imaged 1 day after surgery using the anterior segment module of SD-OCT (OCT Spectralis; Heidelberg Engineering, Heidelberg, Germany). Sclerotomy architecture, including good wound apposition, presence of gaping and misalignment of the roof and floor of the incisions were evaluated. Preoperative, intraoperative and postoperative medical record data were also prospectively collected. Incision gaping and misalignment of the roof and floor occurred more frequently in the superotemporal and superonasal quadrants than in the inferotemporal quadrant (p0.05) and was more frequent in the non-macular group than in the macular group (p0.05). The incidence of incision gaping increased significantly as the incision angle increased. In the macular group, the mean postoperative intraocular pressure (IOP) did not change from the preoperative value, whereas in the non-macular group, the mean IOP decreased significantly from 15.09 ± 2.58 mmHg preoperatively to 12.18 ± 3.25 mmHg on the first postoperative day (p0.005). The mean IOP did not differ significantly between the two groups of surgery at 1 week, and at 1 month postoperatively. In 23-G PPV, non-macular surgery is associated with a significant postoperative IOP decrease in comparison with macular surgery, which could be explained by the most remodelled wound architecture.

Cyclosporine A is a poorly water-soluble, immunosuppressive drug used to treat a variety of ocular diseases. Its limited solubility makes challenging the development of a cyclosporine A-based eye drop for ocular topical application. Based on the prodrug strategy, the practically insoluble cyclosporine A was converted into a freely soluble prodrug. Such a water-soluble prodrug made it possible to develop water-based concentrated eye drops. The prodrug formulations were tested for their ex vivo permeation and in vivo distribution at three concentrations (equivalent to 0.05%, 0.50% and 2.00% w/v cyclosporine A). The ex vivo permeation experiments were performed on corneal and conjunctival epithelia. The in vivo distribution evaluated the total cyclosporine A present in the ocular structures as well as in serum, spleen and cervical lymphatic ganglions. Each prodrug formulation was compared to conventionally used cyclosporine A eye drops at an equivalent concentration. The experimental results showed that the tested eye drops behaved differently. The prodrug formulation was characterized by the following: i) preferential conjunctival penetration, ii) an interesting capacity to create large tissue deposits and iii) a lower risk of systemic complications and immunosuppression. The prodrug aqueous eye drop was demonstrated to be a patient-friendly option for the treatment of ocular diseases requiring high ocular levels of cyclosporine A, pushing the boundaries of the current therapeutic arsenal.

To evaluate the factors affecting the postoperative intraocular pressure (IOP) decrease in 23-gauge (23-G) sutureless vitrectomy, including incision architecture evaluated by anterior segment spectral-domain optical coherence tomography (SD-OCT). A prospective cohort study of 43 patients who underwent primary transconjunctival 23-G pars plana vitrectomy. All sclerotomy wounds were imaged 1 day after surgery using the anterior segment module of SD-OCT (OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany). 23-G sclerotomy architecture, preoperative and postoperative medical data were also prospectively collected. Multivariate logistic regression analysis, with backward elimination, found that surgery duration (adjusted OR = 9.17, p = 0.020) and loss of wound apposition (adjusted OR = 15.12, p = 0.022) were risk factors for significant postoperative IOP decrease (≥3 mmHg) 1 day after surgery; while age, gender, myopia, and gas tamponade were not risk or protective factors for postoperative IOP decrease. In 23-G pars plana vitrectomy, the early postoperative decrease in IOP is mainly influenced by surgery duration and the self-sealing nature of the sclerotomy. The IOP decrease was not influenced by the presence or the absence of gas tamponade.

Purpose To investigate the features of corneal epithelial basement membrane dystrophy using spectral-domain optical coherence tomography (SD OCT) and to examine the reliability of SD OCT in distinguishing epithelial basement membrane dystrophy from the normal cornea. Design Diagnostic test study. Methods Forty-five individuals with epithelial basement membrane dystrophy and 45 age- and sex-matched controls with normal corneas were examined, and SD OCT scans of their corneas were performed. In vivo confocal microscopy was performed to confirm or rule out the diagnosis of epithelial basement membrane dystrophy. The structural corneal changes occurring in eyes with epithelial basement membrane dystrophy based on SD OCT findings were described. Results Epithelial abnormalities were observed in 86 of 87 eyes with epithelial basement membrane dystrophy (45 patients) on SD OCT scans. The 2 main features were the presence of an irregular and thickened epithelial basement membrane duplicating or insinuating into the corneal epithelium layer, or both, and the presence of hyperreflective dots. In some cases, we detected hyporeflective spaces between the corneal epithelial layer and the Bowman layer similar to a corneal epithelial detachment. This corneal epithelial detachment sometimes was associated with a cleavage with a stair-step appearance within the corneal epithelial layer. We found a perfect correlation between in vivo confocal microscopy and SD OCT findings in the diagnosis of epithelial basement membrane dystrophy (κ = 0.98). Conclusions SD OCT provides an accurate assessment of the structural changes occurring in eyes with epithelial basement membrane dystrophy. These changes, visible on SD OCT scans, are easily detectable and permit an accurate diagnosis, especially in patients with no biomicroscopically visible corneal changes.

To evaluate the outcomes of epiretinal membrane (ERM) surgery in highly myopic eyes without traction maculopathy, and to compare them with those from non-highly myopic eyes.Retrospective nested case-control study from a cohort of 509 consecutive patients (509 eyes) who underwent pars plana vitrectomy with ERM removal.Thirty-two highly myopic eyes (with a refractive error of more than -6.00 diopters [D]), which underwent surgery for isolated ERM, were included in the study. For each case studied, we selected from the same cohort 2 age-matched controls who had ERM surgery (n = 64 non-highly myopic eyes). The best-corrected visual acuity (BCVA), the central macular thickness (CMT), and the surgical complications were analyzed.The mean follow-up duration was 3.2 ± 1.5 years for the study cases and 3.4 ± 1.6 years for the control group (P = .608). At the final follow-up examination, the mean logMAR BCVA had improved significantly, from 0.56 to 0.26 (P.001) for the case group and from 0.54 to 0.22 (P.001) for the control group. At the final optical coherence tomography (OCT), the mean CMT had improved significantly, from 433 to 314 μm (P.001) for the case group and from 428 to 303 μm (P.001) for the control group. There was no significant difference between the 2 groups as regards visual or CMT improvement (P = .526 and P = .483, respectively). The incidence of surgical complications was not significant between the 2 groups.The results of ERM surgery were not different in terms of anatomic and visual outcomes and surgical complication between highly myopic and non-highly myopic eyes.