Luca Agnifili

Femtosecond Laser Arcuate Keratotomy for the Correction of High Astigmatism after Keratoplasty

PURPOSE To determine the feasibility and initial outcomes of using a femtosecond laser to perform arcuate keratotomies to correct high post-keratoplasty astigmatism. DESIGN Prospective noncomparative interventional case series. PARTICIPANTS Twelve eyes of 12 consecutive patients (mean age 44.9+/-9.5 years) who presented with a high degree of astigmatism, noncorrectable with spectacles or contact lenses (10 post-penetrating keratoplasty, 2 post-deep lamellar keratoplasty), and were candidates for relaxing incisional corneal surgery. METHODS The Femtec (20/10 Perfect Vision, GmbH, Heidelberg, Germany) femtosecond laser performed paired 90-degree angled arcuate incisions on the graft button. The incision sites and depths were programmed at 1.00 mm inside the graft edge and at 90% of the corresponding local graft thickness, whereas the angular lengths of the cuts were determined by analyzing the locations and extents of the steepest meridians in the topographic map. MAIN OUTCOME MEASURES Changes in uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), mean subjective and topographically determined astigmatism; imaging of incisions by anterior segment optical coherence tomography (AS-OCT); and wound healing by in vivo confocal microscopy (IVCM). RESULTS Postoperative follow-up extended to 6 months. Mean uncorrected logarithm of the minimum angle of resolution (logMAR) BSCVA and UCVA improved from preoperative values of 0.25+/-0.16 and 1.05+/-0.18 to 6-month values of 0.11+/-0.12 (standard deviation) and 0.55+/-0.34, respectively (P<0.05). Mean subjective astigmatism was 7.16+/-3.07 diopters (D) preoperatively and 2.23+/-1.55 D at 1 month after surgery (P = 0.002) and remained stable to the end of follow-up. Anterior segment optical coherence tomography image analysis showed that the depth and location of the incisions were consistent with the preoperative surgical plan. In vivo confocal microscopy showed mild edema and keratocyte activation along the incision edges, together with initial epithelial ingrowth inside the wound, followed by subsequent moderate fibrotic scarring. CONCLUSIONS Arcuate keratotomies performed with the femtosecond laser were effective in reducing post-keratoplasty astigmatism. Laser-generated incisions within the graft button presented precise geometry and reliable depth of incision, with a wound healing pattern characterized by epithelial ingrowth and mild fibrosis. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Filtering Bleb Functionality: A Clinical, Anterior Segment Optical Coherence Tomography and In Vivo Confocal Microscopy Study

PurposeTo provide a microscopic and macroscopic analysis by a clinical, in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) assessment of filtering blebs after glaucoma surgery. Material and MethodsWe retrospectively analyzed 60 eyes of 48 glaucomatous patients by slit-lamp, IVCM, and AS-OCT examinations. Patients were divided into 2 groups: successful blebs (group 1, 16 patients, 27 eyes) were defined as a one-third reduction in preoperative intraocular pressure without antiglaucoma medications and failed blebs (group 2, 32 patients, 33 eyes) as a less than one-third reduction in preoperative intraocular pressure without therapy. The examinations were performed from 1 to 96 months postoperatively. ResultsDiffuse or cystic clinical patterns were indicative for good functionality whereas flat or encapsulation was indicative for poor functionality. When comparing successful with failed blebs, the IVCM analysis showed a greater number (P=0.014), density (P=0.009), and total area of epithelial microcysts (P=0.017) and a lower density of connective tissue (P=0.006). The AS-OCT analysis showed a lower degree of bleb wall reflectivity (P<0.001). A significant correlation was found between the clinical and AS-OCT parameters, particularly for the cystic (100%) and diffuse (74%) patterns. ConclusionsAll IVCM parameters did correlate well with the bleb functionality whereas, among the AS-OCT parameters, only the bleb wall reflectivity was significantly related to the filtering capability. Clinical and AS-OCT bleb classification showed a significant degree of concordance. As a consequence, simultaneous approach by clinical, microscopic, and tomographic assessment improves the clinicians ability in the postsurgery understanding and management of blebs.

Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

Circadian intraocular pressure patterns in healthy subjects, primary open angle and normal tension glaucoma patients with a contact lens sensor

To examine the circadian intraocular pressure (IOP) patterns in healthy subjects, in primary open angle and normal tension glaucoma (POAG; NTG) using a contact lens sensor (CLS; Sensimed Triggerfish, Lausanne, Switzerland).

Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration

Introduction: The consistent association between choroid neovascularization (CNV) and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular age-related macular degeneration (AMD). The authors report the systemic side effects secondary to intravitreal administration of these compounds, that is, the main cardiovascular effects, as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thromboflebitis. Areas covered: The authors reviewed major Clinical Trials and publications concerning systemic adverse events of anti-VEGF drugs in order to identify the main thromboembolic events related to the use of these agents and their occurrence. Anti-VEGF efficacy, safety and tolerability are also discussed. Expert opinion: Three compounds (pegaptanib, ranibizumab and aflibercept) have been approved for the treatment of AMD; a fourth agent, bevacizumab, is used off-label. Anti-VEGF therapy has not shown the ability to fully eradicate the CNV, so that recurrences are common when the intravitreal injections are suspended. Although no evident rise in anti-VEGF-induced thromboembolic side effects was reported, more data are required to evaluate hemodynamic and pharmacokinetics of these compounds. Since only few studies have focused on these aspects, further researches are mandatory to determine distribution, effects and duration of these substances.

An in vivo confocal microscopy and impression cytology analysis of preserved and unpreserved levobunolol-induced conjunctival changes.

Purpose To provide an in vivo confocal microscopy (IVCM) and impression cytology analysis of preserved- and unpreserved levobunolol-induced changes of conjunctival epithelium. Methods 27 eyes of 27 patients were consecutively randomized to receive preserved or unpreserved levobunolol; all patients had a recent diagnosis of primary open angle glaucoma (POAG) or ocular hypertension and were not previously treated with topical medications. IVCM and impression cytology were performed before and after six months of therapy. Goblet cells density and a conjunctival epithelium regularity index were considered in the IVCM analysis, whereas impression cytology specimens were graded and scored in accordance with Nelsons method. Results After six months of therapy, IVCM and impression cytology parameters showed significant differences with respect to baseline in both groups (p<0.001); significant differences were also found between the two groups (p<0.001). The IVCM analysis showed a goblet cells density reduction (61% and 17% from baseline, respectively in group 1 and 2) (p<0.001) and an higher index of epithelial regularity (p<0.001) in both groups; the impression cytology analysis showed an higher score in both groups (p<0.001). Conclusions All the IVCM and impression cytology parameters correlated well with the conjunctival modifications induced by the topical therapy, suggesting the less toxicity of unpreserved drugs

Morphological modification of the cornea after standard and transepithelial corneal cross-linking as imaged by anterior segment optical coherence tomography and laser scanning in vivo confocal microscopy.

Purpose: In vivo analysis of corneal modifications after traditional and transepithelial corneal cross-linking (CXL). Methods: Forty eyes of 35 patients underwent traditional or transepithelial CXL; there was randomization of 20 eyes to each group. By means of in vivo confocal microscopy and anterior segment ocular coherence tomography, we evaluated corneal alterations at 1 week, 1 month, and 3, 6, and 12 months after the treatment. Results: During follow-up, in vivo confocal microscopy showed a significant decrease in anterior keratocyte density (P = 0.001) and more evident stromal edema and keratocyte activation (P = 0.001) in the traditional group, whereas in the transepithelial group, no significant changes were observed (P > 0.05). Anterior segment ocular coherence tomography indicated the presence of hyperreflective stromal line significantly deeper and more persistent in the traditional group (P < 0.001). Conclusions: The preliminary results suggest that traditional CXL induced marked corneal modifications, which were poorly evident in the transepithelial group.

Conjunctival modifications in ocular hypertension and primary open angle glaucoma: an in vivo confocal microscopy study.

PURPOSE The study was conducted to analyze, by in vivo confocal microscopy (IVCM), the conjunctival epithelial characteristics in untreated ocular hypertension (OH) and in topically treated primary open-angle glaucoma (POAG). METHODS The study included 30 eyes affected with untreated OH, 96 eyes with POAG receiving medical therapy, and 15 healthy control eyes. The main outcome measures were the mean density and the mean area of conjunctival epithelium microcysts. The relations among the microscopic parameters intraocular pressure (IOP), and age in both hypertensive and glaucomatous eyes and between mean defect (MD) of visual fields and the time on therapy in patients with glaucoma were analyzed. RESULTS There was no evidence of conjunctival microcysts in any of the healthy eyes examined; conversely, conjunctival microcysts were found in all ocular hypertensive eyes (mean microcyst density of 19.7 +/- 3.5 cysts/mm(2) and mean total microcyst area of 4063.6 +/- 921.2 mum(2)). All patients with POAG showed conjunctival microcysts (mean density of 28.7 +/- 2.7 cysts/mm(2) and a mean total microcyst area of 6564.2 +/- 671.4 mum(2)). No significant differences were found between OH and POAG subjects for microcyst parameters and no significant relations were found in either OH or POAG eyes for microcyst density, area, IOP, MD, and time on therapy. CONCLUSIONS The results of the study show that conjunctival microcysts are features present in all hypertensive and glaucomatous eyes. Based on these findings, conjunctiva could be an additional potential target tissue available for the investigation by a noninvasive in vivo approach of glaucoma-induced pathologic modifications.

In vivo analysis of conjunctiva in gold micro shunt implantation for glaucoma

Aims To describe the conjunctival epithelial features seen with in vivo confocal microscopy (IVCM) after gold micro shunt (GMS) implantation in the suprachoroidal space, in patients with uncontrolled glaucoma. Methods This was an observational case series study. Fourteen eyes of 14 consecutive glaucomatous patients with a history of multiple failed incisional surgeries followed by GMS implantation were evaluated with a digital confocal laser-scanning microscope (HRT II Rostock Cornea Module). Patients were divided into two groups: successful implantations (Group 1: eight patients, eight eyes), defined as a one-third reduction in preoperative intraocular pressure (IOP) with or without antiglaucoma medications and failed implantations (Group 2: six patients, six eyes) as a less than one-third reduction in preoperative IOP with maximal tolerated medical therapy. The examination was performed from 3 to 20 months (mean 15.4±5.4) postoperatively. Conjunctival mean microcyst density (MMD: cysts/mm2) and mean microcyst area (MMA: μm2) were the main outcome measurements. Results The mean postoperative IOP was statistically different between the two groups (p<0.05), with the values of 14.3±2.77 and 32.3±8.01 mm Hg in Groups 1 and 2, respectively. When comparing successful with failed implantation, the IVCM analysis showed a greater MMD (p<0.01) and MMA (p<0.01). Clinical evidence of filtering bleb was not found in any of the patients. Conclusions Successful GMS implantation significantly increased conjunctival microcysts density and surface at the site of the device insertion. These findings suggest that the enhancement of the aqueous filtration across the sclera may be one of the possible outflow pathways exploited by the shunt.

Conjunctival goblet cells density and preservative-free tafluprost therapy for glaucoma: an in vivo confocal microscopy and impression cytology study

Purpose:  To evaluate the density of conjunctival goblet cells (GCs) in glaucomatous patients treated with preservative‐free (PF) tafluprost, using laser scanning confocal microscopy (LSCM) and impression cytology (IC).