From bench to clinic: Emerging therapies for corneal scarring.

Corneal diseases are one of the leading causes of moderate-to-severe visual impairment and blindness worldwide, after glaucoma, cataract, and retinal disease in overall importance. Given its tendency to affect people at a younger age than other blinding conditions such as cataract and glaucoma, corneal scarring poses a huge burden both on the individuals and society. Furthermore, corneal scarring and fibrosis disproportionately affects people in poorer and remote areas, making it a significant ophthalmic public health problem. Traditional medical strategies, such as topical corticosteroids, are not effective in preventing fibrosis or scars. Corneal transplantation, the only effective sight-restoring treatment for corneal scars, is curbed by challenges including a severe shortage of tissue, graft rejection, secondary conditions, cultural barriers, the lack of well-trained surgeons, operating rooms, and well-equipped infrastructures. Thanks to tremendous research efforts, emerging therapeutic options including gene therapy, protein therapy, cell therapy and novel molecules are in development to prevent the progression of corneal scarring and compliment the surgical options currently available for treating established corneal scars in clinics. In this article, we summarise the most relevant preclinical and clinical studies on emerging therapies for corneal scarring in recent years, showing how these approaches may prevent scarring in its early development.

Long-term refractive outcomes and stability after excimer laser surgery for myopia.

PURPOSE: To evaluate the long-term refractive outcomes of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) for myopia. SETTING: Centre for Eye Research Australia, Melbourne, Australia. DESIGN: Comparative case series. METHODS: Preoperative baseline refractions in eyes having PRK, LASIK, or both at 1 multisurgeon center were analyzed from patient databases. Two- to 13-year follow-up data were analyzed and compared with 1-month postoperative visual outcomes. RESULTS: The study evaluated 389 eyes (229 patients). In the PRK group, the mean preoperative spherical equivalent (SE) was -4.05 diopters (D) ± 1.17 (SD) in eyes with low to moderate myopia and -7.97 ± 2.00 D in eyes with high myopia (P = .009) and in the LASIK group, -3.98 ± 1.27 D and -7.64 ± 1.66 D, respectively (P = .008). At the last visit, the mean SE in the PRK group was -0.64 ± 0.83 D in eyes with low to moderate myopia and -1.06 ± 1.74 D in eyes with high myopia (P = .73) and in the LASIK group, -0.33 ± 0.59 D and -0.63 ± 0.90 D, respectively (P = .68). At the end of the study, 45.9% of eyes with low to moderate myopia and 25.0% with high myopia in the PRK group and 64.8% and 37.3%, respectively, in the LASIK group were within ± 0.50 D of the attempted correction. CONCLUSIONS: Laser refractive surgery effectively treated all levels of myopia. Refractive stability was achieved within 1 year postoperatively, with LASIK showing better stability than PRK for up to 6 to 9 years.

Outcomes of laser refractive surgery for myopia.

Many advances have been made in laser refractive surgery, and this review examines how they have affected treatment outcomes in individuals with varying degrees of myopia (law, moderate, and high). Studies with a minimum follow-up of 1 year with at least 2 of the 3 major outcome measures--efficacy, stability, and safety--were reviewed, and how the findings were affected by differences in ethnicity was assessed.

Evaluation of iris recognition system for wavefront-guided laser in situ keratomileusis for myopic astigmatism.

PURPOSE: To evaluate the visual and refractive outcomes of wavefront-guided laser in situ keratomileusis (LASIK) using an iris recognition system for the correction of myopic astigmatism. SETTING: Centre for Eye Research Australia, Melbourne Excimer Laser Research Group, and Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia. METHODS: A comparative analysis of wavefront-guided LASIK was performed with an iris recognition system (iris recognition group) and without iris recognition (control group). The main parameters were uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity, amount of residual cylinder, manifest spherical equivalent (SE), and the index of success using the Alpins method of astigmatism analysis 1 and 3 months postoperatively. A P value less than 0.05 was considered statistically significant. RESULTS: Preoperatively, the mean SE was -4.32 diopters (D) +/- 1.59 (SD) in the iris recognition group (100 eyes) and -4.55 +/- 1.87 D in the control group (98 eyes) (P = .84). At 3 months, the mean SE was -0.05 +/- 0.21 D and -0.20 +/- 0.40 D, respectively (P = .001), and an SE within +/-0.50 D of emmetropia was achieved in 92.0% and 85.7% of eyes, respectively (P = .07). At 3 months, the UCVA was 20/20 or better in 90.0% and 76.5% of eyes, respectively. A statistically significant difference in the amount of astigmatic correction was seen between the 2 groups (P = .00 and P = .01 at 1 and 3 months, respectively). The index of success was 98.0% in the iris recognition group and 81.6% in the control group (P = .03). CONCLUSION: Iris recognition software may achieve better visual and refractive outcomes in wavefront-guided LASIK for myopic astigmatism.

Prevalence of Orbscan II corneal abnormalities in relatives of patients with keratoconus.

BACKGROUND: To determine the prevalence of Orbscan II-derived keratoconus traits in relations of individuals with keratoconus and a control group and to apply these to a pedigree analysis. METHODS: In a controlled, prospective, observational case series, four Orbscan II-derived corneal parameters were examined in relations of individuals with keratoconus and a control group of low myopes (<2.5 D). The four parameters and thresholds for abnormality (derived from a literature review) were as follows: average keratometry (> or =47.2 D), I-S value (> or =1.2 D), posterior float apex (> or =42 microm) and thinnest pachymetry (< or =463 microm). RESULTS: Forty-four unrelated controls (88 eyes) and eight families with 90 members without known (178 eyes) and 11 members with keratoconus (19 eyes) were analysed. One of 88 (1.14%) control eyes had a single keratoconus trait, and none had more than one trait. Of 178 eyes from relatives of patients with keratoconus, 45 (25.3%) had one or more keratoconus traits. Relatives of patients with keratoconus had an elevated risk of possessing a keratoconus trait (relative risk 14.67, CI 2.07-104.07, P < 0.001) compared with controls. Approximately 53.3% of relatives with a keratoconus trait were evident on either pachymetric or posterior elevation indices alone. Six of eight families suggested dominant inheritance. CONCLUSIONS: Keratoconus traits are common in relatives of patients with keratoconus. There prevalence may have been previously underestimated by using placido image-based topography alone where corneal pachymetry and posterior elevation are not assessed. This study suggests an autosomal dominant pattern of inheritance with variable expressivity in some families.

Vision-related quality of life comparison for emmetropes, myopes after refractive surgery, and myopes wearing spectacles or contact lenses.

PURPOSE: To compare the vision-related quality of life among emmetropes, myopes who had refractive surgery, and myopes who wore spectacles and/or contact lenses. METHODS: This cross-sectional study assessed vision-related quality of life using the Vision Quality of Life Index. Participants were age 18 years or older with a presenting visual acuity of 20/40 or better and no other ocular pathology. Responses were compared among three groups: emmetropes (spherical equivalent [SE] < 0.50 to > -0.50 diopters [D]), myopes (SE < or = -0.50 D) who wore spectacles and/or contact lenses, and myopes who had refractive surgery. RESULTS: The study population included 64 emmetropes, 66 myopes who wore spectacles and/or contact lenses, and 65 myopes who had refractive surgery. No significant differences were found between the refractive surgery and emmetropic groups. In contrast, the spectacle and/or contact lens group had significantly increased odds of having concerns about injuring themselves (odds ratio = 11.5, 95% confidence interval [CI] 2.3, 57.1), difficulties coping with demands in life (odds ratio = 23.6, 95% CI 23.8, 198.1), difficulties fulfilling roles (odds ratio = 5.6, 95% CI 1.4, 22.1), and less confidence joining in everyday activities (odds ratio = 30.6, 95% CI 3.2, 292.3) compared to emmetropes. CONCLUSIONS: Myopia corrected with spectacles or contact lenses had a negative impact on some areas of vision-related quality of life. However, individuals with myopia who had refractive surgery enjoyed the same vision-related quality of life as those with emmetropia. The potential improvement in vision-related quality of life should be considered when recommending treatment for myopia.

Evaluation of accuracy in proband-reported family history and its determinants: the Genes in Myopia family study.

PURPOSE: Proband-reported family histories are widely used in epidemiological and genetic studies. The accuracy of these reports may have significant effects on the intended outcome, particularly in genetic studies. This study aims to determine the accuracy of proband-reported family history of myopia and to assess whether demographic or clinical factors are predictive of an accurate history. METHODS: In 2004 to 2005, the study recruited 120 myopic probands (< or = -0.50 D spherical equivalent in both eyes) aged 18 to 72 years and 358 nuclear family members residing within Victoria, Australia as part of the Genes in Myopia (GEM) family study. Data collection used an examiner-administered questionnaire with an ocular examination. Proband-reported family history of myopia was evaluated for agreement with ophthalmic examination results of family members. RESULTS: The statistical measures of accuracy used in this report were sensitivity, specificity, positive predictive value, and negative predictive value. Sensitivity varied from 85 to 98%, specificity from 84 to 96%, positive predictive value from 83 to 97%, and negative predictive value from 84 to 97%. Following multivariate analysis, an evaluation of demographic and clinical factors indicated that the highest predictive accuracy was obtained from proband reporting of their children [odds ratio (OR), 0.38; 95% confidence interval (CI), 0.15 to 0.94] whereas the most inaccurate reporting of a proband was when there was less-severe maternal myopia (per 0.50 D less myopic) (OR, 1.23; 95% CI, 1.06 to 1.43) or for increase in total education of the proband (per 1 year increase) (OR, 1.22; 95% CI, 1.04 to 1.42). CONCLUSIONS: Several variables influence the accuracy of obtaining a family history of myopia. A questionnaire-based approach alone will introduce some error into the study and this should be taken into account when designing and undertaking family-based epidemiological or genetic studies of myopia.

Methodology and recruitment of probands and their families for the Genes in Myopia (GEM) Study.

PURPOSE: Myopia is considered to be a complex disease involving both environmental and genetic factors. The Genes in Myopia (GEM) Study aims to recruit probands with myopia and their family members to allow genetic analysis of myopia to be undertaken. The purpose of this paper is to describe the methodology and recruitment of probands and families for the GEM Study. METHODS: In a sample-based prospective study, 2,095 probands with myopia of -0.50 DS or worse and a positive family history of myopia were contacted via the Melbourne Excimer Laser Group (MELG) database. Probands and family members recruited into the study undertook a detailed assessment including questionnaire, best-corrected visual acuity, objective and subjective refraction, axial length, anterior chamber depth, keratometry readings, slit-lamp examination, height, weight and head circumference measurements, and blood sample collection for DNA analysis. RESULTS: 280 probands with myopia have been recruited into the GEM Study. Probands had a mean age of 49.33 yrs. (SD +/- 11.64) with the average age of myopia onset being 12.58 years (SD +/- 6.71). The average spherical-component refractive error was: right eye -5.13 DS (SD +/- 3.06) and left eye -5.14 DS (SD +/- 3.16). Probands with extreme myopia (-10 DS or worse) showed the highest study participation rate of 56%, when compared to high (-5 DS < -10 DS) (20%), moderate (-3 DS < - 5 DS) (18%) and low myopia (-0.5 DS < -3 DS) (10%). A total of 279 out of 505 (55%) additional family members recruited were also found to be myopic. CONCLUSIONS: The GEM study has used a targeted approach to identify an Australian cohort with a diverse spread of myopia, ranging from low to extreme. Recruitment of probands via the use of an excimer laser practice has proved to be an efficient and economic means of identifying probands with a family history of myopia. In addition, the participation rate in the study appears to vary reflecting a proband's perception of disease severity.