Giuseppe Lamberti

Effect of hinged lamellar keratotomy on postkeratoplasty eyes 1

PURPOSE To evaluate the effect of a hinged lamellar keratotomy on refraction, vision, and corneal topography of postkeratoplasty eyes with high-degree astigmatism. DESIGN Noncomparative, interventional case series. PARTICIPANTS A hinged lamellar keratotomy was performed on nine eyes of nine patients at least 9 months after penetrating keratoplasty and with high-degree astigmatism. All patients were spectacle and contact lens intolerant. INTERVENTION A superiorly hinged lamellar keratotomy (corneal flap), 160 microm in thickness and 9 mm in diameter, was created on all eyes included in this study. Each patient was examined 1 day, 1 month, and 3 months after surgery. MAIN OUTCOME MEASURES Uncorrected visual acuity, best spectacle-corrected visual acuity, refraction, computerized analysis of corneal topography. RESULTS At each postoperative examination time, there was a significant reduction in both average spherical equivalent (P < 0.05) and average absolute value of astigmatism (P < 0.01) over mean preoperative values. The major changes were seen as early as 1 day after surgery, but both progression and regression of the effect were documented at later postoperative examinations. In all patients best spectacle-corrected acuity was maintained or improved after the procedure. Postoperatively, four patients could be successfully corrected either with spectacles (n = 2) or with gas-permeable contact lenses (n = 2). There were no surgical flap or corneal graft complications. CONCLUSIONS Hinged lamellar keratotomy improves vision and refraction of postkeratoplasty eyes with high-degree astigmatism. In some cases it may be so effective as to make planned excimer laser treatment unnecessary.

Idiopathic central retinal vein occlusion in a thrombophilic patient with the heterozygous 20210 G/A prothrombin genotype

PURPOSE To report the occurrence of monolateral central retinal vein occlusion in a patient with heterozygous 20210 G/A prothrombin genotype, known to be associated with high thrombophilic risk. METHODS A monolateral central retinal vein occlusion was diagnosed in a 71-year-old woman, who had suffered from a deep vein thrombosis in her left leg at the age of 36 years. Mutations of the genes involved in the coagulation process were investigated by DNA polymerase chain reaction. RESULT DNA analysis showed the patient to be heterozygous for the prothrombin 20210 G/A genetic variation. CONCLUSION The 20210 G/A prothrombin gene mutation may be associated with central retinal vein occlusion.

The heterozygous 20210 G/A genotype prevalence in patients affected by central and branch retinal vein occlusion: a pilot study

Abstract. Background: Several inherited conditions have been associated with an increased or decreased incidence of retinal vein occlusion (RVO). The A allele in the 20210 G/A prothrombin gene has been found to be associated with systemic venous thrombosis. The aim of this study has been to verify the prevalence of this mutation in patients affected by central RVO (CRVO) or branch RVO (BRVO). Methods: A retrospective study was carried out on 100 consecutive patients suffering from RVO, more than 50 years old, unaffected by systemic diseases known to be associated with markedly increased RVO occurrence. We determined the frequency of this mutation by performing mutagenised amplification of exon 14 followed by restriction analysis of the amplified DNA fragment. Results: The overall frequency of prothrombin 20210A allele in RVO patients was 6.0%. All heterozygous patients had suffered from CRVO. In this study subgroup, the frequency of the 20210 G/A prothrombin heterozygosis was 12.0%. The difference in the frequency of this the genetic variant between the CRVO and BRVO groups was statistically significant. None of the conventional RVO risk factors were statistically related to the occurrence of the disease in either the CRVO or the BRVO subgroup. Conclusion: The prevalence of the prothrombin 20210A mutation observed in CRVO patients is significantly higher than in the normal Italian population. Moreover, the prevalence is significantly greater in CRVO than in BRVO patients. These results raise the possibility that the prothrombin 20210A variant may be considered as a risk factor for CRVO.

Mesectodermal leiomyoma exclusively involving the posterior choroid

PURPOSE To report a mesectodermal leiomyoma of the posterior choroid. DESIGN Observational case report. METHODS A 23-year-old man was referred to us because of a progressive blurred vision in his left eye. Ophthalmologic examination revealed the presence of a 12 x 10 x 7.2-mm amelanotic choroidal mass in his left posterior pole. Fluorescein angiography, A-scan ultrasonography, and B-scan echography findings were suggestive for a diagnosis of choroidal amelanotic melanoma. These clinical features prompted us to enucleate the left eye. RESULTS Histopathological and immunohistochemistry examinations established a definitive diagnosis of mesectodermal leiomyoma of the posterior choroid. CONCLUSION This case represents the first report describing the occurrence of an intraocular mesectodermal leiomyoma that may exclusively involve the posterior choroid.

Endogenous Aspergillus versicolor Endophthalmitis in an Immuno-competent HIV-positive Patient

A 25-year-old white, HIV-positive, immuno-competent man was referred to us because of a progressive blurred vision in his right eye. Clinical characteristics were suggestive for an unilateral fungal endophthalmitis, and thereby fluconazole firstly, followed by conventional amphotericin B were intravenously administered, without any significant improvement. Thus, a pars plana vitrectomy was performed. Aspergillus versicolor was isolated from the cultures of the vitreous sample and intravenous liposomal amphotericin B was administered. An increase of visual acuity together with a reduction of vitreous inflammation occurred. This case of ours represents the first report describing an endogenous endophthalmitis induced by Aspergillus versicolor.

Conjunctival sac fluid contains elevated levels of soluble TRAIL: implications for the anti-tumoral surveillance of the anterior surface of the eye.

Little is known on the ability of different epithelia to release soluble TNF‐related apoptosis‐inducing ligand (TRAIL) and the relevance of TRAIL secretion by epithelial cells is still incompletely understood. On these bases, we have measured the concentration of soluble TRAIL by ELISA in the conjunctival sac fluid. It was the highest ever detected in a biological fluid (mean value of 26,800 pg/ml), being approximately 20‐fold greater than that found in human saliva and >200‐fold greater than that detected in human serum. On the other hand, osteoprotegerin, the soluble decoy receptor of TRAIL, was almost undetectable in the conjunctival sac fluid. Of note, the levels of soluble TRAIL measured in conjunctival sac fluid were in the range able to induce in vitro apoptosis of lymphoma cells. By in situ immunohistochemistry, TRAIL protein expression was predominantly detected in the corneal epithelium and, to a less extent, in the conjunctival epithelium. By flow cytometry analysis, membrane‐associated TRAIL was documented in isolated corneal epithelial cells obtained from patients undergoing photorefractive keratectomy (PRK). The key contribution provided by corneal epithelium to the production of soluble TRAIL was underscored in time‐course experiments, in which a marked decrease of the levels of soluble TRAIL in the conjunctival sac fluid was demonstrated 1 day after PRK followed by a progressive recovery at days 5–30 after PRK. Taken together, our findings strongly support a major role of soluble TRAIL in protecting cornea and conjunctiva from tumor formation and/or invasion. J. Cell. Physiol. 218: 199–204, 2009.

Intraoperative cauterization of the cornea can reduce postkeratoplasty refractive error in patients with keratoconus

OBJECTIVE This study aimed to evaluate the effect of intraoperative corneal cauterization on the postkeratoplasty refraction of patients with keratoconus. DESIGN A randomized clinical trial. PARTICIPANTS Thirty eyes of 29 patients with keratoconus undergoing standard penetrating keratoplasty by the same surgeon were evaluated (MB). INTERVENTION Standard penetrating keratoplasty included the use of an 8.0-mm donor button sutured into a 7.5-mm recipient bed by means of two running 10-0 nylon sutures with 16 bites each. Before trephination of the recipient bed, superficial cauterization causing tissue shrinkage was applied to a 6-mm central area of the cornea of only 15 eyes (group A). The remaining 15 eyes (group B) did not undergo intraoperative cauterization. Before surgery, 6 months, and 13 months after surgery, a complete ophthalmologic examination was performed on each patient, including uncorrected and best-corrected visual acuity, refraction, keratometry, computerized corneal topography, as well as A-scan contact ultrasonography. MAIN OUTCOME MEASURES Postkeratoplasty refractive error was measured. RESULTS Both 6 months (sutures still in place) and 13 months (suture removal performed in all patients) after surgery, the average spherical equivalent was significantly less myopic in the patients undergoing cauterization. At 6 months, it was +1.72 diopters (D) +/- 1.13 D in group A and -3.16 D +/- 2.84 D in group B; at 13 months, it was +0.09 D 1.52 D in group A and -3.89 D +/- 3.01 D in group B. The average keratometric astigmatism also was significantly lower in group A than in group B both at 6 (2.5 D +/- 1.6 D vs. 4.1 D +/- 2.3 D) and 13 months (2.7 D +/- 1.5 D vs. 4.4 D +/- 2.4 D) after surgery. CONCLUSION Cauterization of the central cornea improves the postkeratoplasty refractive results of patients with keratoconus.

Decreased levels of soluble TNF‐related apoptosis‐inducing ligand (TRAIL) in the conjunctival sac fluid of patients with diabetes affected by proliferative retinopathy

Proliferative diabetic retinopathy is associated with progressive retinal capillary activation and proliferation [1]. Proliferative diabetic retinopathy and other proliferative retinopathies are caused by widespread ischaemia of the inner retinal layers, secondary to closure of parts of the retinal capillary bed, leading to new vessel formation in the retina. Proliferative diabetic retinopathy is consideredawoundhealing-like response, in which neovascularization is accompanied by an influx of inflammatory cells and development of myofibroblasts, with fibrovascular contraction causing haemorrhages, retinal detachment and, in the worse cases, blindness [1]. Vascular endothelial growth factor and other pro-angiogenic factors produced by the ischaemic retina are considered to be the major causal growth factor in the neovascularization process [2]. However, other data suggest that negative regulators of angiogenesis, such as pigment epithelium-derived factor, might also interfere with the vascular endothelial growth factorinduced angiogenesis, by down-regulating the PI3K ⁄ Akt pro-survival pathway [3]. A recent study suggested that the tumour necrosis factor (TNF) family member TNF-Related Apoptosis-Inducing Ligand (TRAIL) might also play an important role in restraining endothelial cell proliferation in the retina [4], as TRAIL-deficient mice exhibited delayed regression of retinal neovascularization and recombinant TRAIL-induced apoptosis of retinal endothelial cells [4]. In this respect, a number of studies of our group [5,6] and other groups of investigators (reviewed in Flyvbjerg [7]) have suggested that TRAIL plays an important role in modulating vascular function during diabetes mellitus. In addition, we have recently shown that conjunctival sac fluid contains the highest levels of soluble TRAIL detected in relevant biological fluids [8], which suggested that TRAIL might have an important physiological role in modulating the inflammatory and ⁄ or angiogenic response in the eye. On these bases, in the present study we have investigated the levels of soluble TRAIL in the conjunctival sac fluid of a cohort of patients with diabetes mellitus (n = 60), consisting of 29 patients without retinopathy, 18 patients with non-proliferative diabetic retinopathy and 13 patients with proliferative diabetic retinopathy. The main demographic and clinical features of the patients in the study are reported in Table 1. In particular, the proliferative diabetic retinopathy subgroup included a comparable number of patients with Type 1 diabetes and patients with Type 2 diabetes, who were characterized by a higher incidence of nephropathy and macrovascular angiopathy (Table 1). Standard strips of the Schirmer test were used for absorbing conjunctival sac fluid from each subject, as previously described

TNF-Related Apoptosis Inducing Ligand in Ocular Cancers and Ocular Diabetic Complications

TNF-related apoptosis inducing ligand (TRAIL) is an intensively studied cytokine, in particular for its anticancer activity. The discovery that conjunctival sac fluid contains extremely high levels of soluble TRAIL as compared to other body fluids suggested important implications in the context of the immunological surveillance of the eye, in particular of the anterior surface. In this review, we discuss the potential physiopathologic and therapeutic role of the TRAIL/TRAIL receptor system in a variety of ocular cancers. Moreover, since an increasing amount of data has indicated the important biological activities of the TRAIL/TRAIL receptor systems also in a completely different pathologic context such as diabetes mellitus, in the second part of this review we summarize the currently available data on the involvement of TRAIL in the ocular complications of diabetes mellitus as modulator of the inflammatory and angiogenic response in the eye.

Kinetic Profiles of Inflammatory Mediators in the Conjunctival Sac Fluid of Patients upon Photorefractive Keratectomy

Photorefractive keratectomy (PRK) represents a therapeutic option to remodel corneal stroma and to compensate refractive errors, which involves inflammatory and/or regenerative processes. In this context, the modulation of cytokines/chemokines in the conjunctival sac fluid and their role in the maintenance of the corneal microenvironment during the healing process upon refractive procedures has not been deeply investigated. In this study, serial samples of conjunctival sac fluid of patients (n = 25) undergoing PRK were harvested before and at different time points after surgery. The levels of 29 cytokines/chemokines/growth factors involved in inflammatory/immune processes were measured with a multiplex array system. The results have firstly highlighted the different pattern of cytokine expression between the microenvironment at the anterior surface of the eye and the systemic circulation. More importantly, the kinetic of modulation of cytokines/chemokines at the conjunctival level following PRK revealed that while the majority of cytokines/chemokines showed a significant decrease, MCP-1 emerged in light of its pronounced and significant increase soon after PRK and during the follow-up. This methodological approach has highlighted the role of MCP-1 in the healing process following PRK and has shown a potential for the identification of expression/modulation of soluble factors for biomarker profiling in ocular surface diseases.