Cataract surgery outcome in eyes with keratoconus.

BACKGROUND: To review the refractive outcome of cataract surgery in eyes with keratoconus. METHODS: We retrospectively reviewed the medical records of 64 consecutive patients (92 eyes) who underwent cataract surgery with implantation of a spherical intraocular lens (IOL). We recorded the method of refractive correction and the effect of the keratometry (K) on the biometry prediction error (BPE). RESULTS: 35 eyes had mild keratoconus (mean K<48 dioptres (D)), 40 had moderate keratoconus (mean K 48 D to 55 D) and 17 had severe keratoconus (mean K>55 D). Actual K values were used in all eyes with mild or moderate keratoconus with a target refraction of approximately -1.0 D in mild keratoconus and -1.5 D in moderate keratoconus that resulted in a mean BPE of 0.0 D and +0.3 D, respectively. The actual K values were used in eight of the 17 eyes with severe keratoconus with a mean target refraction of -5.4 D, which resulted in a mean BPE of +6.8 D. In the remaining nine eyes, a standard K value of 43.25 D was used with a mean target refraction of -1.8 D, which resulted in a mean BPE of +0.6 D. CONCLUSIONS: Using the actual K values with a target of low myopia is a suitable option for spherical IOL selection for eyes with a mean K of ≤55 D. When there is severe keratoconus, the use of actual K values can result in a large hyperopic error and the use of standard K value in these eyes should be considered.

Differential effects of costimulatory pathway modulation on corneal allograft survival.

PURPOSE: T lymphocytes have a central role in allograft rejection. On engagement of the T cell receptor by antigenic peptide-major histocompatibility complex (MHC) complex, a second "costimulatory" signal is critical to full T-cell activation or downregulation. In this study, the effect on corneal allograft survival of modulation of the costimulatory molecules programmed death-1 (PD-1) and inducible costimulatory (ICOS) molecule was examined. These molecules are known to modulate, respectively, negative or positive T-cell activation signals. METHODS: A dimeric PD-L1 immunoglobulin (Ig) fusion protein was generated to stimulate the inhibitory receptor PD-1, and a monoclonal antibody was used to block ICOS. The effect of PD-1 engagement and ICOS blockade on lymphocyte activation by in vitro T-cell proliferation and the effect on orthotopic corneal allograft survival in BALB/c mice were determined. RESULTS: Both reagents demonstrated T-cell inhibition in vitro. PD-L1.Ig treatment of BALB/c mice prolonged fully MHC-mismatched C3H donor corneal allograft survival, with a median survival time (MST) of 21 days. This was significantly prolonged compared to isotype control protein-treated recipients (MST 13 days, P < 0.003). Allograft survival in BALB/c recipients treated with anti-ICOS antibody showed no prolongation of survival compared with the isotype control antibody (MST, 12 days in both groups). CONCLUSIONS: Augmented ligation of the PD-1 negative costimulatory molecule significantly prolongs corneal allograft survival. However, in contrast to findings in other allograft models, signaling through the positive costimulatory molecule ICOS appears to be less important in allogeneic rejection of cornea.

Function of indoleamine 2,3-dioxygenase in corneal allograft rejection and prolongation of allograft survival by over-expression.

Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-gamma and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts.

Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel strategy with potential in clinical immunosuppression.

Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complexes (MHCs) and costimulatory signals provided by antigen-presenting cells (APCs). It has been shown that T-cell activation without costimulation can lead to anergy. In this study, we developed a novel strategy to inhibit expression of B7 molecules (CD80/86) by transfecting APCs with a gene construct encoding a modified cytotoxic T lymphocyte antigen 4 (CTLA4) molecule (CTLA4-KDEL) that is targeted to the endoplasmic reticulum (ER). APCs expressing this construct failed to express CD80/86 on their surface, were unable to stimulate allogeneic and peptide-specific T-cell responses, and induced antigen-specific anergy of the responding T cells. Cells expressing CTLA4-KDEL do not up-regulate the indoleamine 2, 3-dioxygenase enzyme, unlike cells treated with soluble CTLA4-immunoglobin (Ig). This gene-based strategy to knock out surface receptors is an attractive alternative to using immature dendritic cells for preventing transplant rejection and treating of autoimmune diseases.

Nasotemporal asymmetry of retinopathy of prematurity.

OBJECTIVE: To quantify an apparent nasotemporal asymmetry in the location of retinopathy of prematurity with respect to the optic disc. METHODS: Twenty-four-bit color images were captured using a contact digital fundus camera during routine screening. Semiautomated measurements were undertaken to determine the distance between the optic disc and retinopathy located in the nasal and temporal regions of the retina. RESULTS: Forty-nine image pairs (17 right eye, 32 left eye) were captured from 10 infants during a period of 32 to 40 weeks postmenstrual age. For right eyes, averaged across age, the mean (SD) distance between the optic disc and temporal retinopathy was 426 (26) pixels and that between the optic disc and nasal retinopathy was 330 (26) pixels. Corresponding measurements for the left eye were 428 (30) and 332 (24) pixels. This observed asymmetry was found to be statistically significant in both left and right eyes (Mann-Whitney U test, P<.01). While the distance between the optic disc and retinopathy increased with age by 10 to 17 pixels per week, the extent of the asymmetry did not vary systematically with age. CONCLUSION: The location of retinopathy of prematurity is asymmetric along the horizontal meridian with respect to the optic disc-an observation germane to retinal vascular development, the pathogenesis of retinopathy of prematurity, and current disease classification by circular (symmetric) zones.