Dysfunctional latent transforming growth factor ß activation after corneal injury in a classical Ehlers-Danlos model.

Patients with classical Ehlers Danlos syndrome (cEDS) suffer impaired wound healing and from scars formed after injuries that are atrophic and difficult to close surgically. Haploinsufficiency in COL5A1 creates systemic morphological and functional alterations in the entire body. We investigated mechanisms that impair wound healing from corneal lacerations (full thickness injuries) in a mouse model of cEDS (Col5a1+/-). We found that collagen V reexpression in this model is upregulated during corneal tissue repair and that wound healing is delayed, impaired, and results in large atrophic corneal scars. We noted that in a matrix with a 50 % content of collagen V, activation of latent Transforming Growth Factor (TGF) ß is dysregulated. Corneal myofibroblasts with a haploinsufficiency of collagen V failed to mechanically activate latent TGF ß. Second harmonic imaging microscopy showed a disorganized, undulated, and denser collagen matrix in our Col5a1+/- model that suggested alterations in the extracellular matrix structure and function. We hypothesize that a regenerated collagen matrix with only 50 % content of collagen V is not resistant enough mechanically to allow adequate activation of latent TGF ß by fibroblasts and myofibroblasts.

Refractive power and biometric properties of the nonhuman primate isolated crystalline lens.

Purpose. To characterize the age dependence of shape, refractive power, and refractive index of isolated lenses from nonhuman primates. Methods. Measurements were performed on ex vivo lenses from cynomolgus monkeys (cyno: n = 120; age, 2.7-14.3 years), rhesus monkeys (n = 61; age, 0.7-13.3 years), and hamadryas baboons (baboon: n = 16; age, 1.7-27.3 years). Lens thickness, diameter, and surface curvatures were measured with an optical comparator. Lens refractive power was measured with a custom optical system based on the Scheiner principle. The refractive contributions of the gradient, the surfaces, and the equivalent refractive index were calculated with optical ray-tracing software. The age dependence of the optical and biometric parameters was assessed. Results. Over the measured age range isolated lens thickness decreased (baboon: -0.04, cyno: -0.05, and rhesus: -0.06 mm/y) and equatorial diameter increased (logarithmically for the baboon and rhesus, and linearly for cyno: 0.07 mm/y). The isolated lens surfaces flattened and the corresponding refractive power from the surfaces decreased with age (-0.33, -0.48, and -0.68 D/y). The isolated lens equivalent refractive index decreased (only significant for the baboon, -0.001 D/y), and as a result the total isolated lens refractive power decreased with age (baboon: -1.26, cyno: -0.97, and rhesus: -1.76 D/y). Conclusions. The age-dependent trends in the optical and biometric properties, growth, and aging, of nonhuman primate lenses are similar to those of the pre-presbyopic human lens. As the lens ages, the decrease in refractive contributions from the gradient refractive index causes a rapid age-dependent decrease in maximally accommodated lens refractive power.

Agreement between optical coherence tomography and digital stereophotography in vertical cup-to-disc ratio measurement.

BACKGROUND: Given the increasing popularity of optical coherence tomography in the diagnosis of glaucoma, we aimed to assess agreement between StratusOCT and stereophotography in measuring the vertical cup-to-disc ratio (VCDR) and examine whether it can be improved by changing the StratusOCT cup-offset. METHODS: In group 1 (79 eyes), VCDR measurements obtained by StratusOCT (using the default cup-offset of 150 microm above the retinal pigment epithelium) and stereophotography were compared. For each eye, the cup-offset was moved upward or downward until the difference disappeared and an adjusted cup-offset was identified. In group 2 (41 eyes), the stereophotography VCDR was compared to the StratusOCT value obtained by using the mean adjusted cup-offset. StratusOCT was used to classify optic disc cups as shallow or deep. RESULTS: In group 1, StratusOCT overestimated VCDR in optic discs with deep cups and underestimated it in those with shallow cups (p < 0.0001). Mean adjusted cup-offsets were 72.8 +/- 92 microm and 191.6 +/- 70 microm for eyes with deep and shallow cups. The 95% limits of agreement (LOA) ranged from -0.21 to 0.17. In group 2, the adjusted cup-offsets enabled us to eliminate the statistical differences in VCDR measurements and improve the 95% LOA (from -0.13 to 0.14). CONCLUSION: Adjusting the StratusOCT cup-offset according to the cup depth improves agreement between StratusOCT and stereophotography in measuring the VCDR.

Biocompatibility of a nonpenetrating synthetic cornea in vascularized rabbit corneas.

PURPOSE: This study was designed to assess feasibility and biocompatibility of a lamellar, nonperforating supraDescemetic Synthetic Cornea (sDSC) implanted in rabbit eyes after a corneal injury. METHODS: Corneal vascularization and scarring was induced in the right eye of 15 rabbits by application of 1-heptanol and complete surgical removal of the limbus. An sDSC (7-mm diameter, 450-microm-thick optical zone, 100-microm-thick outer flange) was implanted after 45 +/- 5 days. The keratoprostheses were implanted with their central optic part positioned on a completely exposed Descemet's membrane (DM) while the outer flange was located in deep stroma. Three different materials were tested: hydrophobic PMMA (n = 5) and hydrophilic HEMA-MMA (n = 5) and HEMA-NVP (n = 5) with a water content of 34% and 75%, respectively. The corneal surface was covered with a conjunctiva-Tenon flap. Central flap trephination was performed after 63 +/- 7 days. DM vascularization and scarring was assessed and graded after flap opening and weekly thereafter. RESULTS: In all 15 consecutive cases implantation could be completed successfully without perforation of DM. Repair of the conjunctival flap had to be performed in five rabbits. Four months postoperatively, the flaps were opened. Four of five corneas (80%) with a PMMA implant and three of five (60%) with a HEMA-NVP75 implant had retained their original transparency. The others had developed significant neovascularization in the Descemet-sDSC optic interface. All corneas (100%) that received an sDSC made of HEMA-MMA34 displayed a completely clear DM without any vessels or scarring. DM was found firmly attached to the posterior surface of the optic. CONCLUSION: Implantation of a nonperforating synthetic cornea on top of an exposed DM is feasible. HEMA-MMA34 showed the most promising results. Because opening of the anterior chamber is not required, a lamellar supraDescemetic Synthetic Cornea would theoretically reduce some of the risks attributed to penetrating keratoprostheses.