Alex Tan

Complement Factor H Y402H and C-Reactive Protein Polymorphism and Photodynamic Therapy Response in Age-Related Macular Degeneration

PURPOSE To investigate the association between complement factor H (CFH) and C-reactive protein (CRP) genotypes and response to photodynamic therapy (PDT) treatment for neovascular age-related macular degeneration (AMD). DESIGN Retrospective cohort study. PARTICIPANTS The study cohort consisted of 273 neovascular AMD patients treated with PDT. METHODS Genotypes were determined for the common T-->C single nucleotide polymorphism (SNP) in exon 9 of the CFH gene (rs1061170; Y402H), as well as 9 selected tagging SNPs across the CRP gene (rs2808635, rs1417938, rs1800947, rs1130864, rs1205, rs3093077, rs876538, rs876537, and rs1572970). Visual acuity outcome after PDT was retrospectively calculated and patients were classified as PDT-positive responders or PDT-negative responders. Logistic regression analysis was used to evaluate the association between individual SNPs and PDT treatment response while adjusting for relevant covariates. MAIN OUTCOME MEASURES Response to PDT treatment defined by visual acuity; genotypes of CFH Y402H and CRP polymorphism. RESULTS Of the 273 patients, 75 had a positive response after PDT treatment. The frequency of CC genotype of the CFH Y402H polymorphism in the PDT-positive response group was lower than in the negative PDT response group (26.4% vs 31.6%) but this difference failed to reach statistical significance. Two CRP SNPs (rs2808635 and rs876538) were significantly associated with PDT treatment response. Positive treatment response was seen in individuals homozygous for the minor allele of the rs2808635 (GG; odds ratio [OR], 3.92; 95% confidence interval [CI], 1.40-10.97; P = 0.048) and rs876538 (AA; OR, 6.49; 95% CI, 1.65-25.47; P = 0.048) variants after adjusting for relevant covariates. The remaining 7 CRP genetic variants did not reveal any significant association with treatment response. CONCLUSIONS Our data did not show significant association between the CFH Y402H polymorphism and PDT treatment response for neovascular AMD; however, CRP genetic variants were associated with a positive response to PDT treatment for neovascular AMD.

Myopia in Young Adults Is Inversely Related to an Objective Marker of Ocular Sun Exposure: The Western Australian Raine Cohort Study

PURPOSE To determine the association between ocular sun exposure measured by conjunctival ultraviolet (UV) autofluorescence and myopic refractive error in young adults. DESIGN Cross-sectional study. METHODS setting: Population-based cohort in Western Australia. study population: Total of 1344 mostly white subjects aged 19-22 years in the Western Australian Pregnancy Cohort (Raine) Eye Health Study. observation procedures: Cycloplegic autorefraction, conjunctival ultraviolet autofluorescence photography, participant questionnaire. main outcome measures: Prevalence of myopic refractive error (spherical equivalent less than -0.50 diopters) and area of conjunctival ultraviolet autofluorescence in mm(2). RESULTS There was an inverse relationship between myopic refractive error and ocular sun exposure, with more than double the prevalence of myopia in the lowest quartile of conjunctival autofluorescence than the highest quartile (33.0% vs 15.6%). Median area of autofluorescence was significantly lower in myopic than in nonmyopic subjects (31.9 mm(2) vs 47.9 mm(2), P < .001). These differences remained significant after adjustment for age, sex, parental history of myopia, and subject level of education. The use of corrective lenses did not explain the lower conjunctival autofluorescence observed in myopic subjects. CONCLUSIONS In this young adult population, myopic refractive error was inversely associated with objectively measured ocular sun exposure, even after adjustment for potential confounders. This further supports the inverse association between outdoor activity and myopia.

Recessive Mutations in SLC38A8 Cause Foveal Hypoplasia and Optic Nerve Misrouting without Albinism

Foveal hypoplasia and optic nerve misrouting are developmental defects of the visual pathway and only co-occur in connection with albinism; to date, they have only been associated with defects in the melanin-biosynthesis pathway. Here, we report that these defects can occur independently of albinism in people with recessive mutations in the putative glutamine transporter gene SLC38A8. Nine different mutations were identified in seven Asian and European families. Using morpholino-mediated ablation of Slc38a8 in medaka fish, we confirmed that pigmentation is unaffected by loss of SLC38A8. Furthermore, by undertaking an association study with SNPs at the SLC38A8 locus, we showed that common variants within this gene modestly affect foveal thickness in the general population. This study reveals a melanin-independent component underpinning the development of the visual pathway that requires a functional role for SLC38A8.

Raine eye health study: design, methodology and baseline prevalence of ophthalmic disease in a birth-cohort study of young adults.

ABSTRACT Purpose: The Raine Eye Health Study (REHS) was conceived to determine the prevalence of and risk factors for eye disease in young adults, and to characterize ocular biometric parameters in a young adult cohort. This article summarizes the rationale and study design of REHS and outlines the baseline prevalence of ophthalmic disease in this population. Methods: The Western Australian Pregnancy Cohort (Raine) Study originated as a randomized-controlled trial of 2900 women recruited from the state’s largest maternity hospital. Their offspring (N = 2868) have been followed at birth, ages 1, 2, 3, 5, 8, 10, 14, 17 and 20 years of age in a prospective cohort study. DNA has been collected from participants for genome-wide association studies. At the 20-year follow-up participants completed a comprehensive eye assessment that included visual acuity, orthoptic assessment and cycloplegic autorefraction, as well as several ocular biometric variables and multiple ophthalmic photographs of the anterior and posterior segments. Results: A total of 1344 participants (51.3% male) were assessed over a 24-month period. For the majority of examined participants (85.5%) both parents were Caucasian, 63.3% had completed school year 12 or equivalent, 5.5% had myopia (spherical equivalent ≤−3 diopters) and 15 participants (1.2%) had unilateral or bilateral pterygia. Keratoconus, cataract, keratitis and uveitis were rare. Conclusion: The REHS design and methodology allow comparison with other population-based studies of eye disease. The study established the prevalence of eye disorders in a large sample of predominantly Caucasian young Australian adults.

Pterygium and conjunctival ultraviolet autofluorescence in young Australian adults: the Raine study.

Sun exposure is associated with several ophthalmic diseases, including pterygium which may develop in adolescence. This study reports the prevalence of pterygium and its associations in a large cohort of young Australian adults. Conjunctival ultraviolet autofluorescence, a biomarker of ocular sun exposure, has recently been characterized in some Australian populations.

Comparison of monochromatic aberrations in young adults with different visual acuity and refractive errors.

Purpose To compare the monochromatic aberrations in a large cohort of 20‐year‐old Australians with differing levels of visual acuity and explore the relationship between these aberrations and refractive error. Setting Lions Eye Institute, Perth, Western Australia, Australia. Design Cross‐sectional analysis of a population‐based cohort. Methods Monochromatic aberrations were measured using a Zywave II wavefront aberrometer with natural pupils in a dark room. The logMAR corrected distance visual acuity (CDVA) was measured monocularly under normal illumination. Cycloplegic autorefraction was also performed. Results The study enrolled 2039 eyes of 1040 participants. Data from 1007 right eyes were analyzed. The median CDVA and spherical equivalent were −0.06 logMAR (interquartile range [IQR], −0.10 to 0.00) and +0.25 diopters (D) (IQR, −0.38 to 0.63), respectively. The median 6.0 mm higher‐order aberration (HOA) was 0.58 &mgr;m (IQR, 0.44 to 0.79). Coma‐like aberrations and 3rd‐, 4th‐, and 5th‐order HOAs were significantly different between subjects with a CDVA of −0.10 logMAR or better and those with a CDVA worse than −0.10 logMAR. Fourth‐order aberrations Z(4,−4) (P=.024) and Z(4,−2) (P=.029) and 2nd‐order aberration Z(2,0) (P<.001) differed significantly between myopic eyes, emmetropic eyes, and hyperopic eyes. Subjects with higher myopia had slightly higher total HOAs. Conclusions The HOAs in this population were marginally higher than previously reported values. The findings confirm there is a difference in monochromatic aberrations between different vision and refractive groups. Results in this study will benefit decision‐making processes in the clinical setting. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Multiple prenatal ultrasound scans and ocular development: 20-year follow-up of a randomized controlled trial

Through comprehensive ophthalmic examination of adult offspring we sought to determine the impact of multiple prenatal ultrasound scans on ocular development.

Bilateral ipilimumab-induced posterior uveitis following treatment for metastatic choroidal melanoma: Letter to the Editor

Ipilimumab is a CTLA-4 monoclonal antibody that amplifies T-cell activation and response to melanoma. It is approved to treat unresectable or metastatic melanoma. Immune-related adverse events are common (up to 90% of patients), and include colitis, hypophysitis, hypothyroidism, hepatitis and dermatitis.1 1.3% of patients suffer from ocular side effects, such as scleritis, anterior uveitis and Graves-type ophthalmopathy.2.