Marina Papadia

A Phase II Study on the Duration and Stability of the Intraocular Pressure-Lowering Effect and Tolerability of Tafluprost Compared With Latanoprost

PURPOSE Tafluprost is a novel prostaglandin F(2alpha)-receptor agonist shown to lower intraocular pressure (IOP) in healthy humans and patients with elevated IOP. We investigated the efficacy, safety, and tolerability of tafluprost 0.0015% compared with latanoprost 0.005% in patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension. METHODS This was a randomized, double-masked, active-controlled, parallel-group, multinational, and multicenter phase II study. Patients received either tafluprost 0.0015% (n = 19) or latanoprost 0.005% (n = 19), both once daily. The extent and duration of action of the IOP-lowering effects at Day 42 and Day 43 were the primary efficacy endpoints. Efficacy and safety parameters were analyzed throughout. RESULTS Maximum IOP reduction was achieved by Day 7 and was sustained until Day 42 in both groups (mean [standard deviation] change from baseline -9.7 [3.3] mm Hg for tafluprost and -8.8 [4.3] mm Hg for latanoprost). The overall treatment group difference was 0.17 mm Hg (95% confidence interval -1.27 to 1.61; P = 0.811). The IOP-lowering effect was maintained for >or=24 h after the last dose in both groups. Most adverse events were ocular and were similar in frequency and severity between groups. There were 3 severe adverse events, all ocular, and all in the tafluprost group (3/19 = 16%). CONCLUSIONS Tafluprost and latanoprost have comparable effects on the extent, duration, and stability of IOP reduction, and are well tolerated in patients.

Tuberculosis-related choriocapillaritis (multifocal–serpiginous choroiditis): follow-up and precise monitoring of therapy by indocyanine green angiography

To report the case of a patient initially diagnosed with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), characterized by relentless evolution despite high-dose steroid therapy. An interferon-gamma release assay (IGRA) indicated a diagnosis of suspected tuberculous choriocapillaritis and the disease responded only to massive inflammation suppressive therapy and antibiotic therapy. Case report. Review of clinical features and investigational procedures. Smoldering relentless evolution and subsequent arrest of progression could be precisely monitored by indocyanine green angiography (ICGA). The patient did not recover after standard anti-tubercolosis (TB) therapy combined with corticosteroid. A fourth antibiotic had to be added in order to stop the progression of the retinal disease. In each case of choriocapillaritis such as APMPPE an infectious cause including TB has to be excluded making IGRA tests unavoidable. As the main structure involved is the choriocapillaris the most precise follow-up or monitoring is obtained with ICGA.

Current and emerging medical therapies in the treatment of glaucoma.

Introduction: Glaucoma is a disease of the eye in which the optic nerve and retinal ganglion cells (RGCs) are injured, leading to the loss of the peripheral visual field and eventually to profound vision loss and blindness. Glaucoma is usually characterized by an increase in intraocular pressure (IOP), which is treated with ocular hypotensive drugs. However, both RGC apoptosis and optic nerve atrophy, due to glaucoma, can occur independently of IOP. Areas covered: This review discusses several current and emerging treatments for glaucoma. Current research is updating the known properties of a number of drugs now used to treat glaucoma. Some drugs may offer neuroprotection, not only reducing vision loss, but restoring injured or compromised RGCs and optic nerve cells. Several molecules now under development aim to lower IOP primarily by enhancing aqueous drainage through conventional pathways of the trabecular meshwork and Schlemms canal. Gene transfer models are being investigated, and a murine-derived neurotrophic growth factor (NGF) seems to offer the promise of actually restoring visual function in some patients. Drugs that are already widely used are being re-branded in preservative-free formulations. Expert opinion: The ultimate goal in glaucoma research is to find new compounds that will not only normalize IOP, but also arrest or even reverse apoptotic damage to the optic nerve and RGCs to slow the rate of progression of the disease so that it will not interfere with the patients ability to see and his/her quality of life. This should be obtained with affordable costs, minimal side effects and a reasonable schedule.

Use of indocyanine green angiography in uveitis.

Investigational imaging of the choroid was limited with only rough information obtained by echography before indocyanine green angiography (ICGA) became available in the 1990s. In posterior uveitis the choroid is involved at least as often, if not more often, than the retina, meaning that, in a large proportion of cases, information was lacking on an entire compartment involved in the inflammatory process. Indeed there are only few conditions such as the Behçet uveitis where significant choroidal involvement can be excluded a priori. In a large proportion of conditions the inflammatory lesion process involves the choroid. Either it starts primarily in the choroid such as in Vogt-Koyanagi-Harada (VKH) disease, birdshot chorioretinitis (BCR), and the primary inflammatory choriocapillaropathies (PICCPs) including, among others, multiple evanescent white dot syndrome (MEWDS) and multifocal choroiditis (MFC), or it can involve the choroid as one of the possible sites of inflammation such as in ocular sarcoidosis or tuberculosis. Choroidal inflammatory involvement, mostly inaccessible to classical imaging such as fluorescein angiography (FA), is largely occult and therefore missed unless ICGA is performed. New types of optical coherence tomography (OCT) devices allow one to measure choroidal thickness as a whole, but cannot identify choroidal stromal inflammatory foci nor do they allow to analyze morphopathologic changes in the thin choriocapillaris. Given the quality of information obtained by ICGA, mostly not available by other imaging techniques, it makes no doubt that ICGA is one of the major investigational imaging modalities in posterior uveitis.

Anatomical and immunological changes of the cornea in patients with pterygium.

Purpose: To test the hypothesis that anatomical and immunological changes are present in the cornea of patients affected by pterygium. Materials and Methods: The central cornea of 20 eyes of 18 patients with primary pterygium was examined by in vivo confocal microscopy using a 40× lens and an axial resolution of 5 μ m. The size of pterygia was measured by analyzing photographic images. Data from 20 age-matched normal subjects were used as control for analysis. Results: The images obtained showed a significant lower number of epithelial cells in patients with pterygium compared to controls, with superficial epithelial cell area considerably higher than normal, reduced nucleus/cytoplasm ratio, halos around the nuclei, and sharp borders. Numerous highly reflective dendritic-like cells were present in the epithelial cell basal layer. The stroma showed a loss of keratocytes and the presence of lacunae. Tortuosity and number of vesicles of sub-basal nerves were significantly higher than controls. The endothelial cell count showed a normal density of cells of this layer. Conclusions: In vivo confocal microscopy may be helpful in evaluating the immunological and structural changes of the cornea in patients with pterygium and understanding its pathophysiology and the possible role of anti-inflammatory therapy.

OCT findings in birdshot chorioretinitis: a glimpse into retinal disease evolution.

BACKGROUND AND OBJECTIVE Birdshot chorioretinitis is a rare disease independently involving the retina and the choroid. Retinal involvement has deleterious functional consequences. This study aimed to follow retinal profiles in early (< 1 year, untreated), intermediate (1 to 6 years, receiving therapy), and late (> 6 years) birdshot chorioretinitis. PATIENTS AND METHODS Optical coherence tomography images were retrospectively evaluated in 28 eyes and retinal thickness was calculated in the foveola, parafoveal nasal, and temporal area; nasal and temporal mid-peripheral macula; and nasal and temporal periphery of the macula. RESULTS Retinal thickness was significantly elevated in early birdshot chorioretinitis because of diffuse exudative retinal vasculopathy. In late disease, retinal thickness was significantly thinned at all measured locations compared with early disease. Epiretinal membrane development was observed in 92% of eyes with late birdshot chorioretinitis. CONCLUSION The retina is thickened and exudative in early birdshot chorioretinitis, thickness diminishes during intermediate birdshot chorioretinitis, and retinal thinning/atrophy with a high rate of epiretinal membrane is observed in late birdshot chorioretinitis.

Obstruction of the Ex-PRESS Miniature Glaucoma Device: Nd

To the Editor: We read with interest the article by Kanner et al about Ex-PRESS implant in glaucomatous patients. The authors reported that in a case series of 345 eyes, the most common devicerelated complication was obstruction of the tube (6 eyes; 1.7%) which was treated successfully by neodimium: yttrium-aluminium-garnet (Nd:YAG) laser. Here, we report a case to highlight the importance of a systematic gonioscopic evaluation of Ex-PRESS implants during follow up and to confirm Nd:YAG laser as a therapeutic option to manage these devices. A patient with primary openangle glaucoma was treated by filtration surgery with placement of an ExPRESS ( 200) device under a scleral flap in his left phakic eye. No complications occurred during surgery. A localized serous choroidal detachment occurred after surgery and resolved when intraocular pressure (IOP) spontaneously normalized after a transient period (2wk) of hypotony. At 3-month follow-up visit, IOP was stable (11mm Hg) and the device was well placed. The patient was sent to our attention again 10 months after surgery because of a gradual increase of IOP in the operated eye. Slit lamp examination revealed a flat bleb and an IOP of 22mm Hg; the anterior chamber was deep and gonioscopy showed a tuft of iris tissue joining and partially plugging the Ex-PRESS (Fig. 1). Nd:YAG laser was performed to break the iris strand at the level of the tip device (Fig. 1); IOP immediately lowered after laser and has been stable (10 to 12mm Hg) up to now. Some studies did not report any cases of obstruction of the Ex-PRESS device; this complication, however, has been reported in both under a scleral or a conjunctival flap implants and also when combined with phacoemulsification procedures. Iris touch without obstruction of the device has also been reported (Fig. 1). In our patient, the Ex-PRESS was well placed and no contact with the iris was detectable. It is not clear how a tuft of iris starting from the iris plane to plug the device could develop; an asymptomatic or undiagnosed late hypotony causing a transient shallowing of the anterior chamber is a possible cause for the iris to get in contact with the implant, thus developing a synechia. Kanner et al reported vitreous as the cause of obstruction in 1 device; no obstruction was directly detectable in the others, although Nd:YAG laser treatment resulted in a dispersion of whitish particles near the tube tip and reduction of the IOP. We confirm that the external blockade of the tube is a possible device-related complication of ExPRESS implants and it should be considered whenever IOP increases and a flat bleb is observed. Nd:YAG laser is a viable therapeutic option to treat the external occlusion of ExPRESS devices, regardless the nature of the obstruction.

Secondary choriocapillaritis in infectious chorioretinitis

Purpose:  To analyse the indocyanine green angiography (ICGA) patterns of hypofluorescence that are compatible with choriocapillaritis that occur secondarily to toxoplasmic retinochoroiditis (ToRC), ocular tuberculosis (including tuberculous choroiditis, TuCR and multifocal serpiginoid choroiditis, TMSC) and syphilitic chorioretinitis (SyCR).

In vivo confocal microscopy in a case of pterygium.

Pterygium is a frequent ocular surface disorder of unknown origin characterized by chronic conjunctival inflammation with a clear central cornea in most patients. A 35-year-old man affected by pterygium in the right eye presented with unremarkable slit-lamp examination of the central cornea, in which in vivo confocal microscopy showed a significant alteration of the superficial epithelial cells, numerous dendritic-like cells in the basal epithelial layer, and loss of keratocytes in the stroma. In vivo confocal microscopy may be helpful in evaluating the immunological and structural changes of the cornea in patients with pterygium and in understanding its pathophysiology.

Antiglaucoma drugs: The role of preservative-free formulations

Hypersensitive reactions to eyedrops are a common finding in clinical practice and represent a frequent cause of discontinuation of the therapy. Moreover, experimental and clinical studies show that long term use of topical drugs may induce ocular surface changes causing discomfort and potentially negatively affecting the compliance to the treatment as well as the success rate of filtering procedures. The exact mechanism involved and the roles of the active compound and the preservatives in inducing such detrimental effects of ophthalmic solutions are unclear. During the last years several antiglaucoma agents have been marketed as either preservative-free or benzalkonium chloride-free formulations in an attempt to reduce the adverse effects related to preservatives. This paper summarizes the body of evidence from existing studies about preservatives in antiglaucoma eyedrops, focusing on the latest compounds commercially available. A systematic review of the literature was performed. Current research is focusing not only on the efficacy of the drugs but also on their tolerability. Based on the existing data, there is a rationale to support the use of benzalkonium-free solutions whenever possible, especially in patients suffering from concomitant ocular surface diseases, experiencing local side effects and in those expected to need multiple and prolonged topical treatments.