Gilles Renard

A second generation of artificial cornea (Biokpro II)

The properties of a new second-generation colonizable artificial cornea were evaluated in humans. The prosthesis consisted of a peripheral rim of a translucent microporous fluorocarbon polymer (expanded polytetrafluoroethylene) fused with the polymer of the central optic. The optic was made of medical-grade polydimethylsiloxane coated with polyvinylpyrrolidone. Its refractive power was 42.2 diopters and it measured 7.0 mm in diameter and 0.55 mm in thickness. The geometry of the optic was tested by high-frequency ultrasound and intraocular pressure and distensibility were measured in an artificial chamber. Prostheses were implanted in one eye of 13 humans. The average follow-up was 6 months (range 3-9 months). Most of the eyes (11/13) were clinically stable after a 7 months follow up. Seven patients had visual acuity improvements. Mean corrected final visual acuity was 20/200 (range, 20/30 to light perception). Five anatomical failures occured (two extrusions, two retroprosthetic membranes, one endophthalmitis). The new optical core, junction, and surface properties of the polymers offer many advantages, quicker colonization of the supporting skirt, and an optical core with a geometry similar to that of a normal human cornea. Epithelial cells did not migrate over the interface and optical core. It seems that formation of an epithelium over the artificial device is essential for the long-term stability of the implant.

Biological effects of hyaluronan in connective tissues, eye, skin, venous wall. Role in aging

Hyaluronan, as most macromolecules of the extracellular matrix, are produced by the differentiated mesenchymal cells. These cells produce also enzymes degrading hyaluronan. This results in the presence of several hyaluronan pools of different molecular weights, all capable of interacting with surrounding cells, mediated by hyaluronan binding proteins and receptors. These interactions modulate cell phenotype and produce a variety of effects conditioning the specific functions of tissues. We shall discuss here several examples studied in our laboratory, concerning skin, cornea and the venous wall. Some of these actions might even be harmful, and could play an important role in aging of connective tissues with loss of function. Some of these age-dependent modifications mediated by hyaluronan will be reviewed and commented, especially the upregulation of matrix degrading enzymes as MMP-2 and MMP-9. We shall also mention some of our experiments for finding molecules capable of counteracting the harmful effects mediated by hyaluronan.

Confocal microscopy in Bowman and stromal corneal dystrophies.

OBJECTIVE To use confocal microscopy to demonstrate the similarity among three autosomal-dominant corneal dystrophies and the diversity of the deposit patterns within a single dystrophy. DESIGN A prospective, comparative case series. PARTICIPANTS Twenty patients (40 eyes) from 10 families suffering from Bowman or stromal dystrophy agreed to take part: 3 with Reis-Bückler dystrophy, 12 with granular dystrophy, and 5 with lattice type-I dystrophy. Of these, nine had recurrence in their grafts or after phototherapeutic keratectomy before the confocal examination. The confocal images of affected corneas were compared with those of ten normal control eyes (ten subjects). INTERVENTION All patients were examined by slit-lamp biomicroscopy. Confocal microscopy was performed with Achroplan 40x/numeric aperture (NA) = 0.75 and 63x/NA = 0.9 water immersion objectives. Image analysis was used to identify the corneal epithelial and stromal deposits correlated with each disorder. MAIN OUTCOMES MEASURES Selected images of the corneal layers were evaluated qualitatively for the size, shape, light scattering, and reflection of the deposits. RESULTS Slit-lamp biomicroscopy showed stromal involvement in all affected eyes. Confocal microscopy identified epithelial deposits in 30% of the eyes and stromal deposits in all eyes. The deposits within the epithelium were revealed more clearly with the 63x/NA = 0.9 objective (higher numeric aperture). Some of the confocal findings near the Bowman layer were common for all three dystrophies. Normal control eyes showed no epithelial or stromal deposits, either by biomicroscopy or confocal microscopy. CONCLUSIONS Confocal microscopy provides an in vivo evaluation of the deposits in the cornea, with a higher resolution than biomicroscopy. The confocal findings common to the three dystrophies may agree with previous hypotheses of the same genetic origin. It may be a useful adjunct to slit-lamp biomicroscopy, particularly when histopathologic studies cannot be performed.

Adventitial sheathotomy for decompression of recent onset branch retinal vein occlusion

Interesting results have been reported on the use of pars plana vitrectomy with adventitial sheathotomy for the decompression of branch retinal vein occlusions (BRVO). Recent onset BRVO responsible for a visual acuity of 20/40 or less have been estimated to be good candidates for this procedure. We report on the results of the prospective evaluation of three eyes (in three patients) with recent onset BRVO which underwent surgical decompression. Three men, aged 40, 50, and 68 years presenting with BRVO for 4, 4, and 3 weeks respectively, underwent surgical decompression. Initial visual acuity was 20/80, 20/80, and 20/200. After 11, 10, and 9 months follow-up, visual acuity was 20/80, 20/200, and 20/200. In two eyes, an increase of the area of retinal non-perfusion was treated with peripheral laser photocoagulation. No cataract, retinal tears or retinal detachment were observed. Conclusion: although feasible, sheathotomy did not lead to a significant visual improvement in our patients. Dissection of the arteriovenous crossing could have induced vascular trauma. Furthermore, vitrectomy with posterior hyaloid detachment alone could be of benefit in the treatment of branched retinal vein occlusions. A prospective randomised trial is needed to assess the effectiveness and the safety of this procedure and to determine the best candidates for surgery.

A new mutation (A546T) of the βig-h3 gene responsible for a French lattice corneal dystrophy type IIIA

PURPOSE To characterize the betaig-h3 gene defect in a French family affected with lattice corneal dystrophy type IIIA (LCDIIIA). METHODS Histologic examination was performed from corneal buttons of two patients. Genomic DNA was extracted from leukocytes, and exons of the betaig-h3 gene were amplified by polymerase chain reaction to be directly sequenced. RESULTS Numerous deposits were evident in the stroma and beneath the Bowman membrane, which had all the features of amyloid deposits. Analysis of exon 12 revealed a heterozygous G to A transition on codon 546. CONCLUSION In contrast to Japanese patients, these French patients affected with LCDIIIA carry a distinct mutation of the betaig-h3 gene (A546T instead of P501T). Therefore, it is unclear whether different mutations could result in the same dystrophy or whether we are dealing with clinical heterogeneity of LCDIIIA.

Damage to the Corneal Endothelium by Minus Power Anterior Chamber Intraocular Lenses

We present 16 phakic myopic eyes (from -10.00 to -25.00 diopters) corrected by minus power intraocular lenses implanted in the anterior chamber whose corneal endothelium was observed by specular microscopy during a postoperative period from 6 to 18 months. Significant morphologic endothelial changes were noted in three eyes along the border of the lens optic. Around dark zones, which appeared acellular, endothelial cells were enlarged, deformed, and separated. These findings may be produced by intermittent contact between the endothelium and lens. Corneal indentation during specular microscopy occasionally caused a curvilinear reflection which corresponded to the optic border. In three eyes, dark areas without cellular abnormality were observed near the curved edge of the lens. These findings probably resulted from the disturbance of the specular reflection on part of the endothelium due to this edge.

Pseudoaccommodation: BioComFold versus a foldable silicone intraocular lens.

PURPOSE To assess the degree of pseudoaccommodation amplitude correlated with shifts along the anteroposterior axis of the BioComFold foldable intraocular lens (IOL). SETTING Department of Ophthalmology, Hôtel-Dieu Hospital, Paris, France. METHODS This prospective study comprised 30 eyes of 30 patients operated on consecutively for cataract by phacoemulsification and in-the-bag implantation of a BioComFold (15 patients) or a foldable control (15 patients) IOL. The BioComFold IOL has a peripheral bulging ring that pushes the optic forward during the effort to accommodate, creating a zoom effect. Pseudoaccommodation amplitude was evaluated using the blurring of controlled vision by adding spheres, with the best correction for distance vision in place. Pupil diameter was measured with a Goldmann campimeter under constant illumination. Anterior chamber depth was determined by A-scan (Paxial, Biophysic Medical) 30 minutes after cyclopentolate 1% was instilled and again 30 minutes after pilocarpine 2% was instilled. RESULTS The difference in pseudoaccommodation amplitude and pupil diameter between the 2 groups was not statistically significant (P = .6737 and P = .4014, respectively). The IOLs forward shifts from maximal ciliary relaxation to maximal ciliary contraction were significantly greater in the BioComFold group (P = .0215). CONCLUSION The design of the BioComFold IOL allowed greater forward optic shifts along the anteroposterior axis during the effort to accommodate. Nevertheless, this shift was not correlated with a significantly greater pseudoaccommodation amplitude.

Clinical outcome of eight BIGH3-linked corneal dystrophies

OBJECTIVE To determine whether the mutational pattern of BIGH3-linked corneal dystrophies (CDs) can accurately predict the clinical course of the disease and be helpful in planning adequate surgical treatment. DESIGN Retrospective noncomparative case series. PARTICIPANTS Chart review of 73 patients (110 eyes) with recently confirmed BIGH3 mutations who underwent a penetrating keratoplasty (PK) from 1978 through 1999. Diagnoses included Thiel-Benhke CD (TBCD/R555Q) (13 eyes), classic granular CD (CGCD/R555W) (28 eyes), superficial variant of granular dystrophy (SVGD/R124 l) (27 eyes), lattice CD type I (LCDI/R124C) (20 eyes), Avellino CD (ACD/R124H) (2 eyes), H626R-lattice dystrophy (LCD/H626R) (6 eyes), and two novel dystrophies: a French variant of granular dystrophy (FVGD/R124 l+DT125-DE126) (9 eyes) and a French lattice CD type IIIA (LCDIIIA/A546T) (5 eyes). METHODS The mutation of the BIGH3 gene was characterized for all patients. Clinical data were reviewed for each patient, and included age at first PK and elapsed time before significant recurrence (as defined by a severe decrease in best-corrected visual acuity related to recurrent deposits in the graft). MAIN OUTCOME MEASURES Mean age at first PK and delay before a significant recurrence. RESULTS Mutational pattern was highly correlated with the clinical course of each dystrophy. According to the genetic mutation, two groups with different prognosis were identified. Group 1 was defined by the presence of the FVGD/R124 l+DT125-DE126 and SVGD/R124 l mutations and was characterized by the early need for treatment and early recurrence of deposits. Group 2 was molecularly defined by the presence of any of the following mutations: LCDI/R124C, CGCD/R555W, LCDIIIA/A546T, TBCD/R555Q, and LCD/H626R. In group 2, mean age at first treatment was older, and delay before a significant recurrence was longer as compared with group 1 (P = 0.0001). CONCLUSIONS These results demonstrate that there is a direct correlation between the molecular defect and the clinical course of BIGH3-linked CDs. They also indicate that molecular characterization of the genetic defect will help predict and design adequate surgical treatment for patients with ambiguous clinical diagnosis.

A Prospective Randomized Trial of Topical Soluble 0.1% Indomethacin Versus 0.1% Diclofenac Versus Placebo for the Control of Pain Following Excimer Laser Photorefractive Keratectomy

BACKGROUND AND OBJECTIVE To compare the safety and efficacy of topical nonsteroidal antiinflammatory drugs (NSAIDs) for the control of pain after excimer laser photorefractive keratectomy (PRK). PATIENTS AND METHODS One hundred twenty informed patients were enrolled in a double-masked, randomized, comparative study and assigned to either 0.1% indomethacin, 0.1% diclofenac, or placebo treatment. Subjective postoperative pain, symptoms, re-epithelialization rate, and systemic medications were monitored for 2 days following photoablation. RESULTS Compared with the placebo, 0.1% indomethacin solution significantly reduced pain on the day of surgery (D0) (P < .05), whereas 0.1% diclofenac did not reach a significant level (P = .46). At D0, analgesic intake by the oral route was significantly greater in the placebo group (P < .05). Severe photophobia was significantly less frequent in the group treated with 0.1% indomethacin (P < .05). Corneal wound healing was significantly delayed in the patients treated with 0.1% diclofenac at D2 as compared with other groups (P = .04). CONCLUSION Topical 0.1% indomethacin solution helps control the pain induced by excimer laser photoablation of the cornea without any detrimental effect to the corneal epithelial wound healing.

A New Fluorocarbon for Keratoprosthesis

Previous studies have demonstrated the potential use of microporous, biocompatible materials to improve the long-term stability of keratoprosthesis. To determine the factors that will influence corneal tissue ingrowth into biocompatible, microporous materials, we have compared three types of fluorocarbon polymers—Impra, Gore-Tex, and Proplast—after intrastromal implantation in rabbit corneas. Despite similar physicochemical structures, a great difference was observed in histologic and ultrastructural cross sections after 4- and 8-month followups. For Gore-Tex, we observed extrusion of the implant and infiltration of necrotic and inflammatory cells. All implants of Proplast also led to significant corneal damage resulting in extrusion of the material. Through the use of electron and light microscopy and image analysis, this study demonstrates the presence of cell differentiation and collagen synthesis in the pores of the Impra implant. Apart from biocompatibility, this experiment demonstrates the influence of pore size, porous microorganization, and biomechanical factors on prosthetic corneal material. Only Impra offers satisfactory interface, allowing fibroblastic cells and neocollagen synthesis into its pores, and it can become transparent