Paolo Frezzotti

An In Vivo Confocal Microscopy Analysis of Effects of Topical Antiglaucoma Therapy With Preservative on Corneal Innervation and Morphology

PURPOSE To evaluate the long-term effects of preservative-free and preservative-containing antiglaucoma eye drops on the tear secretion and ocular surface. DESIGN Comparative retrospective study. METHODS A total of 84 patients with bilateral primary open-angle glaucoma or ocular hypertension divided into 5 groups according to type of topical hypotensive therapy and 20 healthy age-matched volunteers were studied. Clinical tests (corneal sensitivity, Schirmer I test, and lachrymal film break-up time), and in vivo confocal microscopy were performed in all patients. RESULTS A significant reduction of the scores was found between groups on topical hypotensive therapy and the control group in all clinical parameters studied (P < .05). In particular, the clinical scores were significantly lower in the preservative medication groups than in the preservative-free group (P < .05). The density of superficial epithelial cells was reduced in all glaucomatous patients, except for the preservative-free group (P > .05), with respect to control subjects (P < .001). On the contrary, the density of basal epithelial cells of glaucomatous preservative therapy groups was higher than control and preservative-free groups (P < .05). Stromal keratocyte activation and the number of beads were higher in all glaucoma preservative groups (P < .05). The number of sub-basal nerves was lower in all glaucoma groups than in the control group (P < .05) and tortuosity was significantly higher in glaucoma than control groups (P < .05). Reflectivity of fibers did not show any significant difference between the 6 groups (P < .05). CONCLUSIONS Glaucomatous patients with chronic treatment show ocular surface alterations. The development of nontoxic antiglaucoma treatment may reduce damage to the ocular surface and improve the compliance and the adherence in the medical therapy.

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).

Variants in ASB10 are associated with open-angle glaucoma

The molecular events responsible for obstruction of aqueous humor outflow and the loss of retinal ganglion cells in glaucoma, one of the main causes of blindness worldwide, remain poorly understood. We identified a synonymous variant, c.765C>T (Thr255Thr), in ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10) in a large family with primary open angle glaucoma (POAG) mapping to the GLC1F locus. This variant affects an exon splice enhancer site and alters mRNA splicing in lymphoblasts of affected family members. Systematic sequence analysis in two POAG patient groups (195 US and 977 German) and their respective controls (85 and 376) lead to the identification of 26 amino acid changes in 70 patients (70 of 1172; 6.0%) compared with 9 in 13 controls (13 of 461; 2.8%; P = 0.008). Molecular modeling suggests that these missense variants change ASB10 net charge or destabilize ankyrin repeats. ASB10 mRNA and protein were found to be strongly expressed in trabecular meshwork, retinal ganglion cells and ciliary body. Silencing of ASB10 transcripts in perfused anterior segment organ culture reduced outflow facility by ∼50% compared with control-infected anterior segments (P = 0.02). In conclusion, genetic and molecular analyses provide evidence for ASB10 as a glaucoma-causing gene.

Incorporating corneal pachymetry into the management of glaucoma

Intraocular pressure (IOP) results from a dynamic balance between aqueous humor formation and outflow. The simplest technique to measure IOP is indentation tonometry. Another technique is applanation. These methods are related to the elasticity of the eye, which mainly depends on its thickness and hysteresis. For several decades, Goldmann applanation tonometry has been the most accepted method of measuring IOP; the Goldmann tonometer is still used in all important trials. The relationship between IOP values and central corneal thickness (CCT) is well known; Goldmann stated that this relationship only holds for an average corneal thickness of 520 microm measured by optical pachymetry. The Ocular Hypertension Treatment Study (OHTS) showed that CCT is an important risk factor for a change from ocular hypertension to primary open-angle glaucoma. In a multivariate model that included IOP, CCT was the most powerful component of the predictive model. In the Early Manifest Glaucoma Trial (EMGT) with an 11-year follow-up, CCT was a significant predictive factor for glaucoma progression in patients with higher baseline IOP but not in those with lower baseline IOP. Clinical trials such as the OHTS and EMGT cannot prove that CCT is linked to a risk for glaucoma on a biological level. Thus, in eyes with glaucoma, IOP must be treated because it has a significant influence on progression of glaucoma, regardless of the baseline IOP and CCT.

Structural and Functional Brain Changes beyond Visual System in Patients with Advanced Glaucoma

In order to test the hypothesis that in primary open angle glaucoma (POAG), an important cause of irreversible blindness, a spreading of neurodegeneration occurs through the brain, we performed multimodal MRI and subsequent whole-brain explorative voxelwise analyses in 13 advanced POAG patients and 12 age-matched normal controls (NC). Altered integrity (decreased fractional anisotropy or increased diffusivities) of white matter (WM) tracts was found not only along the visual pathway of POAG but also in nonvisual WM tracts (superior longitudinal fascicle, anterior thalamic radiation, corticospinal tract, middle cerebellar peduncle). POAG patients also showed brain atrophy in both visual cortex and other distant grey matter (GM) regions (frontoparietal cortex, hippocampi and cerebellar cortex), decreased functional connectivity (FC) in visual, working memory and dorsal attention networks and increased FC in visual and executive networks. In POAG, abnormalities in structure and FC within and outside visual system correlated with visual field parameters in the poorer performing eyes, thus emphasizing their clinical relevance. Altogether, this represents evidence that a vision disorder such as POAG can be considered a widespread neurodegenerative condition.

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.

Longterm follow‐up of diode laser transscleral cyclophotocoagulation in the treatment of refractory glaucoma

Purpose:  This prospective study was conducted to evaluate the efficacy and safety of transscleral diode laser cyclophotocoagulation (TDLCP) in advanced refractory glaucoma.

Long-term perimetric fluctuation in patients with different stages of glaucoma

Aim To evaluate the long-term perimetric fluctuation (LF) in patients with different stages of glaucoma according to the Glaucoma Staging System 2 (GSS2). Methods This multicentre retrospective study included 161 eyes of 161 stable glaucoma patients undergoing four visual-field tests (Humphrey SITA-Standard program over the central 24° or 30°) over a 2-year period. For each patient, the stage of the disease was classified according to GSS2. LF was then calculated as the mean of the standard deviations of point-to-point threshold sensitivities in the four repetitions. LF in GSS2 stages was compared using the t test. Results LF progressively increased from stage 0 to stage 4, and then decreased at stage 5. Stage 4 had a peak of 3.19±0.94 dB, with statistically significant differences compared with all the other stages. The lowest LF (1.65±0.60 dB) was found for normal subjects, whereas similar data were found for borderline patients and those at stages 1 and 5 (2.09±0.58, 2.13±0.57 and 2.22±0.89 dB, respectively; p>0.13). Visual fields with generalised defects had a lower LF (1.90±0.81) than those with mixed (2.84±0.87, p=0.0003) and localised (2.63±0.72, p=0.004) defects. Conclusions In this study, the authors showed that the lower the visual-field defect, the lower was LF, except at stage 5 of GSS2. As test–retest changes exceeding LF could represent a sign of progression, the authors suggest that clinicians using this classification system calculate LF, in order to better differentiate true progression from variability.

Ocular Surface Changes in Glaucomatous Patients Treated With and Without Preservatives Beta-Blockers

PURPOSE To determine whether there were ocular surface changes in glaucomatous patients treated with preservatives beta-blockers who switched to preservative-free beta-blockers. METHODS This was a prospective, longitudinal, open-labeled study. One hundred thirty-two patients with primary open angle glaucoma treated with a preserved beta-blocker were enrolled. All the patients underwent perimetric and gonioscopic examination, complete ophthalmologic examination, intraocular pressure (IOP) measurements, evaluation of ocular surface, Schirmers test, blood pressure and heart rate at baseline and 1-3 months after changing the medical treatment to a preservative-free timolol 0.1% (Timogel 0.1; Thea). At baseline, after 1 month and at the end of the study (3 months), all patients underwent a questionnaire on the visual quality and symptoms and on the quality of life (QoL). Data were analyzed by t-test when the distribution of the data was normal, by Mann-Whitney when the distribution was not normal. RESULTS No significant difference was found for IOP before switching from preserved beta-blockers to preservative-free ones. No significant difference was found in blood pressure and heart rate. However, a statistically significant difference was found for abnormal fluorescein staining of the cornea and conjunctiva, eyelid erythema, conjunctival hyperemia, and follicular hyperplasia. A significant difference was found for break-up time (from 9.38±4.7 s at baseline to 10.64±4.7 s after 3 months) and Schirmers test (from 12.9±5.96 mm at baseline to 14.2±5.87 mm after 3 months). The questionnaire showed that the patient improved the dryness and foreign body sensation. CONCLUSION In glaucomatous patients, preservative-free 0.1 timolol treatment improved their QoL. Similar dry eye signs or symptoms improved after 3 months of treatment reducing dryness, hyperemia, follicular hyperplasia, and foreign body sensation.

Hydrus microstent compared to selective laser trabeculoplasty in primary open angle glaucoma: One year results

To compare the reduction of intraocular pressure (IOP) and glaucoma medications following selective laser trabeculoplasty (SLT) versus stand‐alone placement of the Hydrus microstent, a microinvasive glaucoma surgery device.