Gian Marco Tosi

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.

Amniotic membrane transplantation in ocular surface disorders

Chronic ocular surface disorders, which can result in severe functional impairment, have been viewed for decades as untreatable diseases. In 1995, the reintroduction of amniotic membrane transplantation (AMT), either alone or associated with limbal stem cell transplantation, has offered new hope of using tissue and cell therapy strategies to repair ocular surface disorders. Amniotic membrane (AM) has been found to exert its effects by acting as a substrate for the growth of ocular surface epithelia, by suppressing inflammation and scarring and by serving as an anti‐microbial barrier. Moreover, AM has recently been used as a substrate for ex vivo expansion of corneal epithelial cells for ocular surface reconstruction. Notwithstanding the substantial agreement among Authors regarding its clinical efficacy, there are still many uncertainties regarding the fate of grafted AM and consequently the mechanisms through which it exerts its long‐term effects. Further studies including controlled clinical trials with numerous cases are required to understand which ocular surface conditions are certain to benefit from AM transplantation and how its mechanical properties interact with the mediators produced to favor ocular surface reconstruction.

Orbital solitary fibrous tumor with aggressive behavior

AbstractBackground.Solitary fibrous tumor (SFT) is a rare spindle cell tumor that arises most often in the visceral pleura; however, a review of the literature shows at least 31 cases occurring in the orbit. Methods.A retrospective case series of three patients with orbital SFT: a 50-year-old man, observed in 1997, with an angioma-like lesion in the upper half of the orbit causing osteolysis of the orbital roof; a 24-year-old man, observed in 1992, with a superotemporal mass in the right orbit occupying the lacrimal gland region, firstly diagnosed as schwannoma, recurring 4 years after dacryoadenectomy; a 70-year-old man, with a retrobulbar mass diagnosed on a biopsy as hemangiopericytoma, recurring and infiltrating the orbital roof 4 years after surgery. Results.A review of the literature and presentation of three cases of SFT which showed infiltration of the orbital roof and/or recurrence. Conclusions.Our cases provide evidence of how orbital SFT can behave aggressively and mimic other orbital tumors, thus making mandatory the consideration of this relatively new entity in common clinical practice as well as careful follow-up. Their aggressive growth is unusual, described in only 6 of the 31 cases so far reported in the literature. Immunohistochemistry is of importance for the diagnosis, since CD34 immunoreactivity is peculiar to SFT.

Preliminary results of cataract extraction with implantation of a single-piece AcrySof intraocular lens

Purpose: To evaluate the intraoperative and postoperative performance of the single‐piece AcrySof® SA30AL intraocular lens (IOL) in a series of patients after cataract surgery and IOL implantation. Setting: Department of Ophthalmology and Neurosurgery, University of Siena, Siena, Italy. Methods: In this prospective study, 20 patients who had phacoemulsification and implantation of a single‐piece AcrySof SA30AL lens from March to April 2000 were evaluated. Assessed were control of IOL folding, ease of IOL implantation, IOL centration, intraoperative and postoperative complications, visual acuity, and anterior (ACO) and posterior (PCO) capsule opacification. Results: In all cases, the IOL was easily folded, inserted, and unfolded. It remained well centered in the capsular bag, and there were no intraoperative or postoperative complications. The best corrected visual acuity after surgery was 20/40 or better in all patients. No eye developed ACO or phimosis. One eye had a well‐demarcated, oval area of lens epithelial cell proliferation on the posterior capsule that did not impair visual acuity. Conclusions: Initial results indicate that the single‐piece AcrySof SA30AL IOL has good biocompatibility, haptic flexibility and resistance, and stability in the capsular bag. The incidence of PCO in 1 eye could have been the result of several factors and requires further evaluation. An area of future study is the wide haptic of the lens, which may create a path for cells to proliferate as they travel from the equatorial capsule.

Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: implications for pathogenesis and therapeutic approach.

Human retinoblastoma occurs in two forms (familial and sporadic) both due to biallelic mutation of the RB1/p105 gene even if its loss is insufficient for malignancy. We have recently reported that loss of expression of the retinoblastoma-related protein pRb2/p130 correlates with low apoptotic index, suggesting that RB2/p130 gene could be involved in retinoblastoma. Mutational analysis of RB2/p130 in primary tumors showed a tight correlation between Exon 1 mutations and pRb2/p130 expression level in sporadic retinoblastoma. These mutations are located within a CpG-enriched region prone to de novo methylation. Analysis of RB2/p130 methylation status revealed that epigenetic events, most probably consequent to the Exon 1 mutations, determined the observed phenotype. Treatment of Weri-Rb1 cell line by 5-Aza-dC induced an increase in expression level of pRb2/p130, E2F1, p73 and p53. Overall, our results highlight a crucial role of epigenetic events in sporadic retinoblastoma, which opens a perspective for new therapeutic approaches.

Amniotic membrane graft: Histopathological findings in five cases

Amniotic membrane transplantation (AMT) is an effective treatment for ocular surface reconstruction; however, the mechanisms through which amniotic membrane (AM) exerts its effects as well as its fate after transplantation have not been entirely elucidated and have been investigated only in part. We evaluate the integration of AM in the host cornea in five patients who underwent AMT as the result of Bowens disease, band keratopathy, radio‐ or cryotherapy‐induced keratopathy, chemical burn or post‐herpetic deep corneal ulcer with descemetocele. Due to persistent opacification in four cases and a progressing tumor in one case, penetrating keratoplasty (PK) and enucleation were performed as early as 2 months and up to 20 months after AMT. The corneas were analyzed histopathologically. To evaluate AM remnants, corneas were stained with periodic acid Schiffs reaction (PAS), Alcian blue, and Gomory and Masson trichrome; immunostaining including collagens III and IV antibodies was also performed. None of the corneas showed remnants of AM. In all cases, we observed discontinuity of Bowmans membrane. In three cases, the corneal epithelium was completely restored, ranging from three to six cell layers. In the other two cases, we detected an intense inflammatory reaction with rich neovascularization; the epithelial surface of the central cornea was completely restored, while at the periphery of the cornea goblet mucus‐producing cells were present. Although clinically useful in all cases, restoration of a stable corneal epithelium through AMT is limited by the extent and severity of limbal stem cell deficiency (LSCD). The lack of histologically documented AM remnants in our cases seems to explain the efficacy of AMT more through its biological properties than through its mechanical properties.

Corneal collagen cross-linking to stop corneal ectasia exacerbated by radial keratotomy.

Purpose: To assess the efficacy of riboflavin ultraviolet A (UV-A) corneal collagen cross-linking in the management of keratoconic corneal ectasia exacerbated by radial keratotomy (RK). Methods: A patient with progressive corneal ectasia and hyperopic shift, occurring 10 years after RK performed in the left eye, was treated with riboflavin UV-A corneal collagen cross-linking according to the Siena protocol: Pilocarpin 0.1% drop (1 hour before), lidocaine 4% drops 15 minutes before, mechanical scraping of epithelium (9-mm-diameter area), preirradiation stromal soaking for 10 minutes in riboflavin 0.1%-dextrane 20% (Ricrolin; Sooft Italy) applied every 2 minutes, and 30 minutes of total exposure (6 steps of 5 minutes) to solid-state UV-A illuminator (Caporossi, Baiocchi, Mazzotta Vega X linker; CSO Opthalmics, Florence, Italy), energy delivered 3 mW/cm2, and irradiated area 9 mm in diameter. Results: After the operation, uncorrected visual acuity and best spectacle-corrected visual acuity improved from 0.2 to 0.6 and from 0.3 to 0.8 Snellen lines, respectively, in a 12-month follow-up. Improved topographical K readings and corneal symmetry index were also recorded starting from the first postoperative month and continuing thereafter. No adverse effects were recorded after treatment. Conclusions: Riboflavin UV-A-induced corneal cross-linking seems to be a promising surgical option in the management of unstable corneal ectasia exacerbated by RK, particularly in eyes with preexisting keratoconus. A large cohort and longer follow-up are needed to determine its long-term efficacy in this clinical setting.

Geographic variation and environmental conditions as cofactors in Chlamydia psittaci association with ocular adnexal lymphomas: a comparison between Italian and African samples.

A particular extra‐nodal lymphoma type arises from B cells of the marginal zone (MZ) of mucosa‐associated lymphoid tissue (MALT). The aetiology of MZ lymphomas suggests that they are associated with chronic antigenic stimulation by microbial pathogens, among which Helicobacter pylori‐associated gastric MALT lymphoma is the best studied. Recently, MALT lymphomas have been described in the context of chronic conjunctivitis, which can be associated with Chlamydia spp. infection. Studies from Italy showed the presence of Chlamydia psittaci in 87% of ocular adnexal lymphomas (OAL), and C. psittaci has been described in a large part of samples from Austria and Korea as well. However, this finding was not always confirmed by other studies, suggesting that the association with C. psittaci may depend on geographic heterogeneity. Interestingly, none of the studies up to now has been carried out in the African population, where a strong association between infectious agents and the occurrence of human neoplasms has been reported. This study was designed to investigate the possible association of Chlamydia psittaci in cases retrieved from Kenya, compared to cases from Italy. Our results showed that there was a marked variation between the two geographical areas in terms of association with C. psittaci, as 17% (5/30) of the samples from Italy were positive for C. psittaci, whereas no association with this pathogen was observed in any of the African samples (0/9), suggesting that other cofactors may determine the OAL occurrence in those areas. OAL cases are often characterized by down‐regulation of p16/INK4a expression and promoter hypermethylation of the p16/INK4a gene. Our results showed a partial methylation of p16/INK4a promoter in C. psittaci‐negative cases, whereas no hypermethylation of this gene was found in C. psittaci‐positive cases, suggesting that mechanisms other than promoter hypermethylation lead to p16/INK4a silencing in C. psittaci‐positive cases. We may conclude that the role of epidemiologic, environmental and genetic factors, must be considered in the aetiology of this disease. Copyright

Diagnosis and management of traumatic cyclodialysis cleft

A 48-year-old man presented with hyphema, iridocyclitis, iridophacodonesis, and maculopathy after a contusive trauma. Ultrasound biomicroscopy identified a 90-degree cyclodialysis cleft with severe damage of the zonular fibers. Echographic B-scan examination revealed intravitreal hemorrhage and a 360-degree choroidal detachment. One month later, phacoemulsification was performed and a single-piece poly(methyl methacrylate) intraocular lens was inserted into the ciliary sulcus, with the haptic rotated toward the cyclodialysis cleft area. Postoperatively, the visual acuity improved and the intraocular pressure returned to normal. Ultrasound biomicroscopy showed closure of the cleft by reattachment of the ciliary body to the scleral spur. Optical coherence tomography revealed complete resolution of the macular and choroidal folds. Ultrasound biomicroscopy is a useful method for appropriate management of traumatic cyclodialysis cleft. In cases of small cyclodialysis clefts, with the surgical method we describe, the lens haptics apply directional force toward the sclera, fostering adherence of the ciliary body fibers.

Long-term results of combined 1-way phacoemulsification, intraocular lens implantation, and trabeculectomy

PURPOSE To analyze the results of 1-way phacoemulsification and posterior chamber intraocular lens (IOL) implantation combined with trabeculectomy. SETTING Department of Ophthalmology and Neurosurgery, University of Siena, Siena, Italy. METHODS This retrospective study comprised 42 eyes of 36 patients with glaucoma and cataract who had phacoemulsification with posterior chamber IOL implantation combined with trabeculectomy. The mean follow-up of 28.24 months +/- 10.99 (SD) (range 11 to 52 months) included measurement of intraocular pressure (IOP), visual acuity, visual field, endothelial cell loss, and notation of complications. RESULTS There was a statistically significant postoperative improvement in visual acuity (P < .001). Mean preoperative best corrected visual acuity (BCVA) was 20/200 (range 20/30 to hand movements). Mean 1 year postoperative BCVA was 20/30 (range 20/20 to 20/60). The preoperative mean IOP of 24.06 mm Hg decreased to 15.36 mm Hg at 1 year (P < .001). All 42 eyes had a postoperative IOP of less than 21.00 mm Hg. Mean central cornea endothelial cell density preoperatively was 2238 +/- 396 cells/mm2 (range 1697 to 2906 cells/mm2) and postoperatively, 2005 +/- 397 cells/mm2 (range 1302 to 2801 cells/mm2). Early postoperative complications consisted of a choroidal detachment in 2 patients (4.76%). Three and 4 days after surgery, respectively, 2 patients (4.76%) had surgery to remove viscoelastic substance under the IOL. Late complications included posterior synechias in 3 eyes (7.14%). One year after surgery, because of a significant decrease in vision, a neodymium:YAG laser posterior capsulotomy was necessary in 2 eyes, 1 with an acrylic IOL (3.70%) and 1 with a silicone lens (9.09%). CONCLUSION Combined phacoemulsification, posterior chamber IOL implantation, and trabeculectomy was safe and effective in patients with coexisting glaucoma and cataract.