Vincenzo Fasanella

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.

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

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).

Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naïve to therapy

Primary open angle glaucoma (POAG) is one of the main causes of irreversible blindness worldwide. The pathogenesis of POAG is still unclear. Alteration and sclerosis of trabecular meshwork with changes in aqueous humor molecular composition seem to play the key role. Increased intraocular pressure is widely known to be the main risk factor for the onset and progression of the disease. Unfortunately, the early diagnosis of POAG still remains the main challenge. In order to provide insight into the patho-physiology of glaucoma, here we report a shotgun proteomics approach to tears of patients with POAG naïve to therapy. Our proteomics results showed 27 differential tear proteins in POAG vs. CTRL comparison (25 up regulated proteins in the POAG group and two unique proteins in the CTRL group), 16 of which were associated with inflammatory response, free radical scavenging, cell-to-cell signaling and interaction. Overall the protein modulation shown in POAG tears proves the involvement of biochemical networks linked to inflammation. Among all regulated proteins, a sub-group of 12 up-regulated proteins in naïve POAG patients were found to be down-regulated in medically controlled POAG patients treated with prostanoid analogues (PGA), as reported in our previous work (i.e., lipocalin-1, lysozyme C, lactotransferrin, proline-rich-protein 4, prolactin-inducible protein, zinc-alpha-2-glycoprotein, polymeric immunoglobulin receptor, cystatin S, Ig kappa chain C region, Ig alpha-2 chain C region, immunoglobulin J chain, Ig alpha-1 chain C region). In summary, our findings indicate that the POAG tears protein expression is a mixture of increased inflammatory proteins that could be potential biomarkers of the disease, and their regulation may be involved in the mechanism by which PGA are able to decrease the intraocular pressure in glaucoma patients.

In vivo confocal microscopy of meibomian glands in glaucoma

Aim To investigate, using laser scanning confocal microscopy (LSCM), the morphological changes of meibomian glands (MGs) in patients with glaucoma. Methods A total of 80 patients who were glaucomatous were enrolled, and 20 healthy subjects were used as controls. After completing an Ocular Surface Disease Index (OSDI) questionnaire, all subjects underwent tear film break-up time (BUT), fluorescein staining, Schirmer test I (STI) and LSCM examination of the MGs. The main outcome measures were: eyelid margin epithelial cell density, mean acinar density (MAD) and area (MAA), glandular orifice area, secretion reflectivity and inhomogeneous appearance of interstice and acinar wall. Results According to the number of anti-glaucoma medications they were taking, patients were divided into three groups: group 1 (30 eyes), one drug; group 2 (23 eyes), two drugs; group 3 (27 eyes), three or more drugs. LSCM showed lower MAD and MAA, greater secretion reflectivity and glandular orifice area in groups 2 and 3 than in controls (p<0.05). The inhomogeneity of the interstice and acinar wall was significantly greater in all groups compared to controls (p<0.05). Preserved prostaglandin analogues (PGAs) induced more pronounced modifications of all parameters than preservative free (PF)-PGAs (p<0.05). No significant differences were found between preserved and PF-β-blockers. Significant relations were found among MAD, MAA, secretion reflectivity and OSDI score, BUT and ST (p<0.05) and between secretion reflectivity and orifice area (p<0.001). Conclusions In vivo LSCM is an effective tool in revealing morphological changes of MGs induced by anti-glaucoma medications. Given the key role in the ocular surface health, the evaluation of MG status in patients who are glaucomatous is worthwhile.

Conjunctival characteristics in primary open-angle glaucoma and modifications induced by trabeculectomy with mitomycin C: an in vivo confocal microscopy study

Objectives: To evaluate the microscopic epithelial features seen with in vivo confocal microscopy (IVCM) of bulbar conjunctiva in glaucomatous patients undergoing trabeculectomy with mitomycin C in order to elucidate modifications. Methods: Fifteen eyes of 15 consecutive Caucasian patients affected with primary open-angle glaucoma (POAG) undergoing trabeculectomy and 10 eyes of 10 glaucomatous patients (controls) under medical therapy were enrolled. Eyes were examined using a digital confocal laser-scanning microscope (HRT II Rostock Cornea Module) at baseline and after 6 weeks. The mean microcyst density (MMD: cysts/mm2) and microcyst area (MMA: μm2) were the main outcome measurements. Results: Before surgery, the mean intraocular pressure (IOP) was 25.1 (SD 3.2) mm Hg. MMD and MMA were 22.4 (11.9) and 4696.0 (3608.1), respectively. After trabeculectomy, the mean IOP was 16.1 (1.7) mm Hg. A marked increase in both MMD and MMA, with values of 103.1 (22.6) and 29 489.3 (12 954.9), respectively, was observed. In the control group at baseline, the mean IOP was 15.7 (1.9) mm Hg, and the microcyst parameters did not differ from eyes undergoing filtering surgery. After 6 weeks, IOP and microcysts parameters did not show any significant modifications. Conclusions: Conjunctival epithelial microcysts were demonstrable in glaucomatous eyes under medical therapy prior to trabeculectomy. The filtering procedure increased microcysts density and surface at bleb site indicating a marked postsurgical enhancement of aqueous filtration across conjunctiva.