In Vivo Analysis of Prostaglandins-induced Ocular Surface and Periocular Adnexa Modifications in Patients with Glaucoma.

BACKGROUND/AIM: Prostaglandin analogues (PGAs) are a first-line medical treatment for glaucoma because of their powerful intraocular pressure (IOP) lowering effect, few systemic side-effects (SEs), and the once daily administration. Despite the high systemic safety profile, the chronic use of PGAs may induce periocular and ocular surface (OS)-related side effects, which affect a significant proportion of glaucomatous patients. In this review, we summarize the current knowledge about SEs of PGAs on periocular structures and OS, and their implications in clinical practice. MATERIALS AND METHODS: A comprehensive literature search on the PubMed platform was performed. Two hundred fifty articles fulfilling key words were identified, of which 180 were excluded since they did not concern the effects of PGAs on the periocular tissues and OS, or because of their limited relevance. The following key words were used and combined, to narrow-down the literature: "prostaglandin" and "ocular surface," which identified 184 unique publications, of which 68 were selected; "prostaglandin" and "periocular" which identified 46 unique publications, of which 11 were selected. An additional search was conducted using "prostaglandin" and "Meibomian glands (MGs)", which identified twenty unique publications, of which 8 were selected. Thus, a total of 70 articles were chosen based on their relevance and were included in this review. RESULTS: Prostaglandin-associated peri-orbitopathy, skin pigmentation and hypertrichosis, eyelash growth, and MGs dysfunction are the most frequent modifications of periocular tissues. They are induced by the tissue accumulation of PGAs, and FP receptor stimulation. Without preservatives, PGAs act as stimulators of conjunctival goblet cells, which are the main source of ocular surface mucoproteins, and seem to increase conjunctival epithelium microcysts proposed as in vivo hallmark of the trans-scleral aqueous humour outflow. Additional PGA-induced modifications can be recognized in the cornea, corneo-scleral limbus, conjunctival stroma and, conjunctiva-associated lymphoid tissue, mainly appearing as inflammatory changes. OS epithelia desquamation, chemosis, apoptosis, dendritic cell activation, conjunctival or episcleral vasodilation, and sub-basal nerve plexus disruption were also described in patients receiving preserved PGAs. CONCLUSION: PGAs induce several modifications of the OS structures and adnexa; nonetheless, none of them significantly reduces the local safety profile of this class of drugs. Moreover, the OS changes do not affect the IOP lowering efficacy of PGAs. On these bases, local SEs of PGAs should not discourage clinicians in using this class of medications because of their efficacy, the systemic safety profile, and the better adherence.

Three-dimensional Laser Scanning Confocal Analysis of Conjunctival Microcysts in Glaucomatous Patients Before and After Trabeculectomy.

BACKGROUND/AIM: In glaucoma, conjunctival epithelial microcysts (CEM) have been extensively investigated by means of laser scanning confocal microscopy. In the present case series, we examined eight glaucomatous patients undergoing trabeculectomy to obtain a 3-dimensional (3-D) characterization of CEM. MATERIALS AND METHODS: Image acquisition was performed in z-scan automatic volume mode by Heidelberg Retina Tomograph III/Rostock Cornea Module and a series of 40 images of 300×300 µm (384×384 pixels) to a maximum depth of 40 µm were acquired throughout the upper bulbar conjunctiva before (at the site planned for surgery) and eight weeks after trabeculectomy. The 3-D volume tissue reconstruction with maximal size of 300×300×40 µm was obtained. RESULTS: In the enface view, CEM appeared as empty, optically clear, round or oval shaped sub-epithelial structures. The 3-D spatial reconstruction showed microcysts as oval-shaped and optically clear elements, which were close, but clearly separated from the epithelium. CEM were embedded in the extra-cellular spaces and located about 10 µm below the epithelial surface. After trabeculectomy, CEM increased density and area especially along the horizontal axis. CONCLUSION: The 3-D in vivo confocal reconstruction of CEM permits for better clarification of their microscopic anatomy and patho-physiological significance, confirming their involvement in AH flow through the bleb-wall after filtration surgery for glaucoma.

Advance in the pathogenesis and treatment of normal-tension glaucoma.

Normal-tension glaucoma (NTG) is a multifactorial disease where mechanical stresses and vascular alterations to the optic nerve head probably represent the key pathogenic moments. Although intraocular pressure (IOP) plays a crucial role in the retinal ganglion cell loss, the IOP reduction does not necessarily reduces the disease progression. Therefore, several IOP-independent factors such as glutamate toxicity, oxidative stress, autoimmunity, and vascular dysregulation have been considered in the pathogenesis of NTG. Numerous evidences documented an impairment of the ocular blood flow, involved both in the onset and progression of the disease. The IOP reduction remains the main strategy to reduce the damage progression in NTG. Recently, new treatment strategies have been proposed to improve the control of the disease. Neuroprotection is a rapidly expanding area of research, which represents a promising tool. In the present review, we summarize the recent scientific advancements in the pathogenesis and treatment of NTG.

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.

Topographically guided two-step LASIK and standard LASIK in the correction of refractive errors after penetrating keratoplasty.

PURPOSE: To evaluate in a long-term period the effectiveness and safety of topographically guided two-step laser in situ keratomileusis (LASIK) and standard LASIK technique in the correction of refractive errors after successful penetrating keratoplasty (PKP) for keratoconus. METHODS: At least 2 years after PKP and 6 months after removal of all sutures, 15 eyes of 15 patients (Group 1; mean manifest refraction spherical equivalent (MRSE) -7.23 D -/+ 3.42 SD) were submitted to standard LASIK and 15 eyes of 15 patients (Group 2; mean MRSE -4.37 D -/+ 1.97 SD) to a topographically guided two-step LASIK procedure (first the flap and at least 2 weeks later the laser ablation). In all cases, a superior hinged corneal flap(160 microm/9.5 mm) was created. RESULTS: After a follow-up of 36 months, in Group 1 the mean uncorrected visual acuity (UCVA) was 0.51 logarithm of the minimum angle of resolution (logMAR) -/+ 0.41 SD and the mean best-corrected visual acuity (BCVA) was 0.03 logMAR -/+ 0.05 SD, with a mean MRSE of -1.57 D -/+ 2.65 SD. In Group 2, the mean UCVA was 0.28 logMAR -/+ 0.24 SD and the mean BCVA was 0.01 logMAR -/+ 0.03 SD, with a mean MRSE of -0.07 D -/+ 1.00 SD. In both groups, no complications were observed. CONCLUSIONS: After a long follow-up period, both topographically guided two-step LASIK and standard LASIK could be considered effective and safe tools in the correction of refractive errors after successful PKP for keratoconus.

Enhancement outcomes after photorefractive keratectomy and laser in situ keratomileusis using topographically guided excimer laser photoablation.

PURPOSE: To evaluate the efficacy and safety of topographically guided excimer laser photoablation to retreat unsuccessful myopic and hyperopic photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). SETTING: Eye Clinic, San Salvatore Hospital, University of L'Aquila, L'Aquila, Italy. METHODS: At least 3 months after primary PRK (Group A) or primary LASIK (Group B), 48 eyes of 42 patients were submitted to PRK or LASIK enhancements. The eyes were treated with an excimer laser linked to a computerized videokeratography unit with a topographically supported customized ablation workstation. RESULTS: The mean follow-up was 27.8 months +/- 8.2 (SD). In Group A, the uncorrected visual acuity (UCVA) changed from 0.5 +/- 0.7 logarithm of the minimum angle of resolution (logMAR) (range 20/600 to 20/200) to 0.1 +/- 0.7 logMAR (range 20/60 to 20/20); the mean best spectacle-corrected visual acuity (BSCVA) changed from 0.1 +/- 0.7 logMAR (range 20/50 to 20/20) to 0 +/- 0.7 logMAR (range 20/50 to 20/20) after the enhancement. In Group B, the UCVA changed from 0.7 +/- 0.8 logMAR (range 20/600 to 20/40) to 0.1 +/- 0.7 logMAR (range 20/40 to 20/20); the mean BSCVA improved from 0.2 +/- 0.8 logMAR (range 20/30 to 20/20) to 0 +/- 1.3 logMAR (range 20/25 to 20/20) after surgery. CONCLUSIONS: The enhancements using topographically guided excimer laser photoablation with a topographically supported customized ablation method resulted in satisfactory and stable visual outcome with good safety and efficacy after unsuccessful PRK and LASIK.