Angelo Balestrazzi

Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans.

Purpose: To assess ultrastructural stromal modifications after riboflavin-UVA-induced cross-linking of corneal collagen in patients with progressive keratoconus. Methods: This was a second-phase prospective nonrandomized open study in 10 patients with progressive keratoconus treated by riboflavin-UVA-induced cross-linking of corneal collagen and assessed by means of Heidelberg Retinal Tomograph II Rostock Corneal Module (HRT II-RCM) in vivo confocal microscopy. The eye in the worst clinical condition was treated for each patient. Treatment under topical anesthesia included corneal deepithelization (9-mm diameter) and instillation of 0.1% riboflavin phosphate-20% dextran T 500 solution at 5 minutes before UVA irradiation and every 5 minutes for a total of 30 minutes. UVA irradiation was 7 mm in diameter. Patients were assessed by HRT II-RCM confocal microscopy in vivo at 1, 3, and 6 months after treatment. Results: Rarefaction of keratocytes in the anterior and intermediate stroma, associated with stromal edema, was observed immediately after treatment. The observation at 3 months after the operation detected keratocyte repopulation in the central treated area, whereas the edema had disappeared. Cell density increased progressively over the postoperative period. At ∼6 months, keratocyte repopulation was complete, accompanied by increased density of stromal fibers. No endothelial damage was observed at any time. Conclusions: Reduction in anterior and intermediate stromal keratocytes followed by gradual repopulation has been confirmed directly in vivo in humans by HRT II-RCM confocal microscopy after riboflavin-UVA-induced corneal collagen cross-linking.

Corneal Healing After Riboflavin Ultraviolet-A Collagen Cross-Linking Determined by Confocal Laser Scanning Microscopy In Vivo: Early and Late Modifications

PURPOSE To assess early and late micromorphological modifications of cross-linked corneas in vivo by means of Heidelberg Retinal Tomography (HRT) II confocal microscopy. DESIGN Prospective nonrandomized open trial. METHODS Micromorphological examination of 44 cross-linked keratoconic corneas was performed in vivo by HRT II confocal laser scanning microscopy. Riboflavin ultraviolet (UV)-A-induced corneal collagen cross-linking (CXL) was performed according to the Siena protocol: pilocarpin 1% drops 30 minutes before, topical anesthesia with lidocaine 4% drops 15 minutes before irradiation, mechanical scraping of epithelium (9-mm-diameter area), preirradiation soaking for 10 minutes in riboflavin solution 0.1% (Ricrolin, Sooft, Italy) applied every 2.5 minutes for 30 minutes, 30 minutes exposure to solid-state UVA illuminator (Caporossi; Baiocchi; Mazzotta, X-linker, CSO, Italy), 8-mm-diameter irradiated area, energy delivered 3 mW/cm(2). All patients were examined by confocal scans preoperatively and at the following times after treatment: one, three, and six months, and one, two, and three years. RESULTS No damage to the limbal region was observed. Epithelial regrowth was complete after four days of soft contact lens bandage. The anatomy of the subepithelial plexus was restored one year after the operation with full corneal sensitivity. Increased density of extracellular matrix in late postoperative period indicated cross-linked collagen to a depth of 340 microm expressed by a late demarcation line. CONCLUSION In vivo confocal microscopy showed early and late modification of corneal microstructure after the treatment. The three-year stability of CXL recorded could be related to increased cross-links formation, synthesis of well-structured collagen and new lamellar interconnections.

Stromal haze after combined riboflavin-UVA corneal collagen cross-linking in keratoconus : in vivo confocal microscopic evaluation

The technique of corneal collagen cross‐linking consists of photopolymerization of stromal fibres by the combined action of a photosensitizing substance (riboflavin or vitamin B2) and ultraviolet light from a solid state UVA source. Photopolymerization increases the rigidity of corneal collagen and its resistance to keratectasia. In this report we present two cases, studied through in vivo confocal microscopy, with stage III keratoconus that developed stromal haze after the cross‐linking treatment.

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.

Riboflavin-UVA-induced corneal collagen cross-linking in pediatric patients

Purpose: Evaluation of stability and functional response after riboflavin-UVA–induced cross-linking in a population of patients younger than 18 years with progressive keratoconus after 36 months of follow-up. Methods: Prospective nonrandomized phase II open trial conducted at the Department of Ophthalmology, Siena University, Italy. The “Siena CXL Pediatrics” trial involved 152 patients aged 18 years or younger (10–18 years) with clinical and instrumental evidence of keratoconus progression. The population was divided into 2 groups according to corneal thickness (>450 and <450 μm) at the time of enrollment. The riboflavin-UVA–induced corneal cross-linking was performed in all patients according to the standard epi-off protocol. Parameters recorded preoperatively and postoperatively were as follows: uncorrected visual acuity, best spectacle–corrected visual acuity, corneal topography and surface aberrometry (CSO Eye Top topographer; Florence, Italy), optical pachometry (Visante OCT; Zeiss Meditec, Jena, Germany), and HRT II confocal microscopy (Rostock Cornea Module, Heidelberg, Germany). Results: Functional data at 36 months showed an increase of +0.18 and +0.16 Snellen lines for uncorrected visual acuity and best spectacle-corrected visual acuity, respectively, in the thicker group (corneal thickness >450 μm) and +0.14 and +0.15 Snellen lines, respectively, in the thinner group (corneal thickness <450 μm). Patients in the latter group already showed a better and faster functional recovery than the thicker group at 3-month follow-up. Topographic results showed statistically significant improvement in K readings and asymmetry index values. Coma reduction was also statistically significant. Conclusions: The study demonstrated significant and rapid functional improvement in pediatric patients younger than 18 years with progressive keratoconus, undergoing riboflavin-UVA–induced cross-linking. In pediatric age, a good functional response and keratoconus stability was obtained after corneal cross-linking in a 36-month follow-up.

Photodynamic Therapy with Verteporfin for Symptomatic Circumscribed Choroidal Hemangioma: Five-Year Outcomes

OBJECTIVE To evaluate the long-term efficacy of verteporfin photodynamic therapy (PDT) as the primary treatment for symptomatic circumscribed choroidal hemangioma (CCH). DESIGN Prospective consecutive, 2-centered, noncomparative, interventional case series. PARTICIPANTS Twenty-five subjects with symptomatic CCH. All patients had recent onset of visual symptoms and evidence of exudative macular changes on fluorescein angiography (FA) and optical coherence tomography (OCT). METHODS Verteporfin 6 mg/m(2) body surface area was administered intravenously over a 10-minute interval. Five minutes after infusion, a 689 nm laser was applied with a light dose of 50 J/cm(2) for the first 3 patients and a light dose of 100 J/cm(2) for all the other patients. Retreatments were performed in case of persistent exudation found on OCT. Evaluation of best-corrected visual acuity (BCVA) using Early Treatment of Diabetic Retinopathy Study (ETDRS) criteria, FA, indocyanine green angiography (ICGA), OCT, and ultrasound were performed before PDT and on follow-up examinations. All patients were followed for at least 5 years. MAIN OUTCOME MEASURES Primary outcome measures were changes in BCVA and foveal center thickness (FCT) between baseline and month 60. Secondary measures were tumor thickness decrease, absence of leakage on FA, and adverse events. RESULTS Twenty-two patients received 1 PDT session at 100 J/cm(2), and no recurrences were detected. Three eyes, treated with 50 J/cm(2), received a second PDT session at 100 J/cm(2) 1 month after the first session. After a follow-up of 60 months, BCVA improved an average of 18.5 ETDRS letters (P<0.001); BCVA improved by > or =2 lines in 19 eyes (76%). The FCT decreased from a mean of 386.20 microm to 179.2 microm, and OCT showed the complete resolution of macular exudation in all cases. All tumors responded with a reduction in size. No treatment-related adverse events or complications were identified. CONCLUSIONS The 5-year results of PDT in treating symptomatic CCH support treatment with a light dose of 100 J/cm(2) after slow intravenous infusion of verteporfin to stabilize or improve visual acuity and resolution of macular exudation.

Deep lamellar keratoplasty with trypan blue intrastromal staining.

This technique was developed to facilitate removal of the deep stromal layers during deep lamellar keratoplasty. A trypan blue 0.02% solution is injected into the stromal fibers, enabling the surgeon to visualize and remove the posterior stromal layers. This decreases the risk of perforation of Descemets membrane and the endothelium.

Factors Predicting Unsuccessful Big Bubble Deep Lamellar Anterior Keratoplasty

Purpose: To evaluate the role of corneal structural resistance as a surgical failure factor in deep lamellar keratoplasty (DLK). Method: A total of 10 eyes of 10 patients underwent DLK at the Ophthalmic Hospital in Rome. The big bubble technique was performed for deep stromal dissection by air injection. Seven patients were affected by advanced keratoconus and corneal thinning ranging from 441 to 235 µm. Two patients were affected by central corneal opacity from herpetic keratitis, and one patient suffered from corneal leucoma caused by bacterial keratitis. Clinical follow-up comprising final astigmatism and visual acuity findings were evaluated with a minimum follow-up of 12 weeks. Results: DLK was successfully performed in eight eyes, five of which were affected by moderate to advanced keratoconus and three by post-infective corneal opacity. In these patients preoperative ultrasonic pachymetry ranged between 441 and 287 µm. In the remaining two patients a perforation of the Descemet’s membrane (DM) occurred while attempting to separate it from the overlying stroma by the big bubble technique, requiring a penetrating keratoplasty (PK) to be performed. In both cases preoperative ultrasonic pachymetry was below 250 µm. Both perforations occurred at a different site than the needle site and at the operative time of the big-bubble injection. Discussion: An ultrastructurally weakened DM may suffer a loss of resistance to a stressing force, becoming unable to tolerate the big bubble technique, and thus being perforated. Since the weakening of the DM is related to end-stage keratoconus corneal thinning, the preoperative corneal thickness rather than the surgeon’s ability can play a major role in surgical failure of DLK. Our study reveals a very high risk of perforation of the DM when pre-operative total pachymetry is below limit of 250 µm.

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.