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BACKGROUND: To explore the risk factors for failure of bilateral medial rectus muscle recession (BMR) for esotropia. METHODS: We reviewed 171 consecutive patients with esotropia who underwent bilateral medial rectus muscle recession as a primary procedure from January 2009 to December 2011. Patients with infantile, partially accommodative and acquired esotropia were included. We compared patients who required more than one surgery to patients who only had one operation. RESULTS: A total of 171 patients (89 males, 52%, mean age 5.1 ± 6.0 years, range 0.4-51 years) fulfilled the inclusion criteria and comprised the study population. Mean follow-up period was 17.4 ± 15.5 months (range 1-65 months). A second strabismus surgery was performed in 17 (9.9%) cases within a mean time of 11.7 ± 9.2 months (range 0.4-27.7 months) from the initial surgery. Univariate analysis demonstrated that in patients younger than 1 year the odds ratio (OR) of failure was 4.00 (95% CI 1.12-14.35, p = 0.033) and for patients older than 7 years the OR of surgical failure was 3.27 (95% CI 1.10-9.76, p = 0.033). In addition, patients with esotropia > 60 prism diopters (PD) had a trend towards needing further surgery (OR = 3.91, 95% CI 0.93-16.44, p = 0.063). A multivariate model of regression revealed that age and angle of esotropia > 60 PD remained significant risk factors for requiring additional surgeries. CONCLUSIONS: In our cohort of patients who underwent BMR for esotropia, a large angle of esotropia and age were associated with failure of surgery and need for reoperation.

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IMPORTANCE: Ocular surface disease (OSD) is common and can reduce treatment compliance and quality of life. BACKGROUND: To determine whether a punctal plug improves OSD and reduces intraocular pressure (IOP) in patients using prostaglandin analogue monotherapy. DESIGN: Randomized controlled trial. PARTICIPANTS: Sixty eligible subjects aged >18 years with symptomatic OSD from glaucoma clinics were invited to participate. Lacrimal or glaucoma surgery, lid malposition and contact lens wear were exclusion criteria. METHODS: One eye received an inferior punctal plug, leaving the fellow eye as a control. MAIN OUTCOME MEASURES: Ocular surface disease index (OSDI), tear film breakup time (TF-BUT), Oxford cornea score, tear osmolarity and IOP were compared at baseline and 6 weeks by masked investigators. RESULTS: From 60 eligible, 48 (80.0%) participated (mean age 69.6 years; 60.0% female). OSDI reduced following plug insertion (mean difference [MD] 14.5, 95% confidence interval [CI] 5.06-23.94, P < 0.001). Compared to control eyes, in eyes receiving plugs the TF-BUT increased (MD 2.3 s, 95% CI 1.4-3.2, P < 0.001), the Oxford cornea score decreased (MD 0.5, 95% CI 0.3-0.7, P < 0.001), and tear osmolarity decreased (MD 10 mOsm/L, 95% CI 3.5-16.5, P = 0.003). Punctal plugs resulted in a significantly lowered IOP (MD 1.5 mmHg, 95% CI 0.1-2.9, P = 0.032). Sub-group analyses showed similar efficacy regardless of prostaglandin preservative status or lubricant drop use. Plugs were well tolerated but extrusion occurred in 8.5%, and epiphora increased in 6.5% eyes. CONCLUSIONS AND RELEVANCE: Punctal plug insertion improves subjective and objective measures of OSD and results in a reduced IOP in patients with symptomatic ocular surface disease using prostaglandin analogue monotherapy.

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BACKGROUND/AIMS: To determine the mortality within 20 years of diagnosis of chronic open-angle glaucoma (COAG) and visual acuity and visual field progression of a cohort followed for 20 years. METHODS: Twenty years following the diagnosis of COAG in 68 of 436 (16%) patients seen in a glaucoma case-finding clinic, visual and mortality outcomes were audited from medical records. Causes of death were obtained from general practitioner records and death certificates. Probability of death was calculated using a Kaplan-Meier survival curve. The visual field of each eye of survivors was graded using a nine-stage severity scale. Visual outcome was analysed at the 20-year follow-up visit. RESULTS: From 68, 14 (21%) were lost to follow-up. In the remaining 54, 20 (37%) were alive 20 years after diagnosis. Of 63% who died, mean age of death was 84 years, most commonly due to vascular disease. Mean age at presentation of those who died was 73.7 years versus 63.2 years for survivors (P=0.001). The median time to death was 16 years. On visual field analysis, nearly half (48.9%) of eyes did not deteriorate, but 28.3% eyes deteriorated by more than two stages. Those who died had worse final visual acuity than survivors (P<0.001). Three who died were registered severely visually impaired mainly from macular disease, but no survivors were registered (P<0.001). CONCLUSION: In this cohort, approximately two-thirds of patients with glaucoma died within 20 years of diagnosis. In most older patients with glaucoma, the overall goal of preventing visual handicap and blindness is achievable 20 years after diagnosis.

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Primary open-angle glaucoma (POAG) is influenced by both genetic and environmental factors. Despite significant progress in identifying genetic variants associated with POAG, there remains a substantial amount of unexplained heritability. Study design features that may enhance knowledge of the genetic architecture include focusing on multiple quantitative traits related to ocular disorders (i.e. endophenotypes), targeting genetic variants that directly influence gene expression (i.e. cis-eQTLs) and utilising genetically isolated populations to reduce genetic and environmental noise and thus enhance association signals. In this study we performed heritability and blood-based eQTL association analysis of five key POAG endophenotypes in 330 individuals from the Norfolk Island (NI) isolate. Results showed evidence of heritability for all five traits, with H2 estimates ranging from 0.35 for intraocular pressure (IOP) to 0.82 for central corneal thickness (CCT) (P < 0.05). The primary finding was for BTN3A2, whereby both cis-SNP and transcript were significantly associated with disc size within a conditional regression model. Specifically, this model included rs853676 (ß = 0.23,P = 0.008) and transcript (ß = 0.23, P = 0.03). We also observed a cis-SNP association between optic disc size and LPCAT2 independent of transcript (P = 0.0004). These genes have specific functions in immune system pathways and suggest a role for an inherited immune component of POAG risk. This study also demonstrates an alternate approach to understanding the functional genetic basis of POAG and ocular health more generally.

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PURPOSE: Primary open-angle glaucoma (POAG) refers to a group of heterogeneous diseases involving optic nerve damage. Two well-established risk factors for POAG are elevated intraocular pressure (IOP) and a thinner central corneal thickness (CCT). These endophenotypes exhibit a high degree of heritability across populations. Large-scale genome-wide association studies (GWASs) of outbred populations have robustly implicated several susceptibility gene variants for both IOP and CCT. Despite this progress, a substantial amount of genetic variance remains unexplained. Population-specific variants that might be rare in outbred populations may also influence POAG endophenotypes. The Norfolk Island population is a founder-effect genetic isolate that has been well characterized for POAG endophenotypes. This population is therefore a suitable candidate for mapping new variants that influence these complex traits. METHODS: Three hundred and thirty participants from the Norfolk Island Eye Study (NIES) core pedigree provided DNA. Ocular measurements of CCT and IOP were also taken for analysis. Heritability analyses and genome-wide linkage analyses of short tandem repeats (STRs) were conducted using SOLAR. Pedigree-based GWASs of single-nucleotide polymorphisms (SNPs) were performed using the GenABEL software. RESULTS: CCT was the most heritable endophenotype in this cohort (h2 = 0.77, p = 6×10-6), while IOP showed a heritability of 0.39 (p = 0.008). A genome-wide linkage analysis of these POAG phenotypes identified a maximum logarithm of the odds (LOD) score of 1.9 for CCT on chromosome 20 (p = 0.0016) and 1.3 for IOP on chromosome 15 (p = 0.0072). The GWAS results revealed a study-wise significant association for IOP at rs790357, which is located within DLG2 on chr11q14.1 (p = 1.02×10-7). DLG2 is involved in neuronal signaling and development, and while it has not previously been associated with IOP, it has been associated with myopia. An analysis of 12 known SNPs for IOP showed that rs12419342 in RAPSN on chromosome 11 was nominally associated in Norfolk Island (NI; p = 0.0021). For CCT, an analysis of 26 known SNPs showed rs9938149 in BANP-ZNF469 on chromosome 16 was nominally associated in NI (p = 0.002). CONCLUSIONS: These study results indicate that CCT and IOP exhibit a substantial degree of heritability in the NI pedigree, indicating a genetic component. A genome-wide linkage analysis of POAG endophenotypes did not reveal any major effect loci, but the GWASs did implicate several known loci, as well as a potential new locus in DLG2, suggesting a role for neuronal signaling in development in IOP and perhaps POAG. These results also highlight the need to target rarer variants via whole genome sequencing in this genetic isolate.

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BACKGROUND: The vitreous is the clear jelly of the eye and contains fine strands of proteins. Throughout life the composition of this vitreous changes, which causes the protein strands in it to bundle together and scatter light before it reaches the retina. Individuals perceive the shadows cast by these protein bundles as 'floaters'. Some people are so bothered by floaters that treatment is required to control their symptoms. Two major interventions for floaters include Nd:YAG laser vitreolysis and vitrectomy. Nd:YAG laser vitreolysis involves using laser energy to fragment the vitreous opacities via a non-invasive approach. Vitrectomy involves the surgical replacement of the patient's vitreous (including the symptomatic vitreous floaters) with an inert and translucent balanced salt solution, through small openings in the pars plana. OBJECTIVES: To compare the effectiveness and safety of Nd:YAG laser vitreolysis to pars plana vitrectomy for symptomatic vitreous floaters. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 17 January 2017), Embase Ovid (1947 to 17 January 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 17 January 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 17 January 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 17 January 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 17 January 2017. We did not use any date or language restrictions in the electronic searches for trials. We also searched conference proceedings to identify additional studies. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) that compared Nd:YAG laser vitreolysis to pars plana vitrectomy for treatment of symptomatic floaters. DATA COLLECTION AND ANALYSIS: We planned to use methods recommended by Cochrane. The primary outcome we planned to measure was change in vision-related quality of life from baseline to 12 months, as determined by a vision-related quality of life questionnaire. The secondary outcomes we planned to measure were best corrected logMAR or Snellen visual acuity at 12 months for the treated eye(s) and costs. Adverse outcomes we planned to record were the occurrence of sight-threatening complications by 12 months (asymptomatic retinal tears, symptomatic retinal tears, retinal detachment, cataract formation, and endophthalmitis). MAIN RESULTS: No studies met the inclusion criteria of this review. AUTHORS' CONCLUSIONS: There are currently no RCTs that compare Nd:YAG laser vitreolysis with pars plana vitrectomy for the treatment of symptomatic floaters. Properly designed RCTs are needed to evaluate the treatment outcomes from the interventions described. We recommend future studies randomise participants to either a Nd:YAG laser vitreolysis group or a vitrectomy group, with participants in each group assigned to either receive treatment or a sham intervention. Future studies should follow participants at six months and 12 months after the intervention. Also they should use best corrected visual acuity (BCVA) using an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart read at 4 metres, vision-related quality of life (VRQOL), and adverse outcomes as the outcome measures of the trial.

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Variation in systemic hydration status, namely chronic systemic hypohydration or dehydration, can influence the development of several chronic non-ophthalmic diseases. Owing to the eye's high water content and unique system of fluid regulation, we hypothesized that hydration status may affect the eye in health and disease states. Therefore, we performed a systematic review of the current evidence implicating changes in hydration and their association with ocular physiology and morphological characteristics. We also reviewed relevant clinical correlations of changes in hydration and major common eye diseases. Our findings suggest that systemic hydration status broadly affects a variety of ocular pathophysiologic processes and disease states. For example, dehydration may be associated with development of dry eye syndrome, cataract, refractive changes and retinal vascular disease. On the other hand, excessive hydration is associated with some ocular diseases. Tear fluid osmolarity may be an effective marker of systemic hydration status. Recent studies implicate chronic renin-angiotensin-aldosterone system activation in the pathogenesis of diabetic retinopathy and glaucoma but also suggest its antagonism may be a useful therapeutic target. Our findings indicate that assessment of hydration status may be an important consideration in the management of patients with chronic eye diseases and undergoing eye surgery. Further research investigating the role of acute and chronic changes in hydration in individuals with and without ocular disease is warranted.

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PURPOSE: Astigmatism is a common cause of refractive error and is known to vary in prevalence with age. Although the search for genes associated with spherical refractive errors (especially myopia) has met with limited success, current efforts to identify genetic variants implicated in astigmatism development have been less rewarding. We aimed to assess the association between astigmatism and age to identify appropriate age cut-offs for maximizing power in genetic studies of astigmatism. METHODS: We performed a cross-sectional analysis of right eye astigmatism data from four Australian-based eye studies comprising 3841 participants aged 5-90 years. Measurements were performed under cycloplegia using an autorefractor, and individuals with a history of cataract, refractive surgery or corneal pathology were excluded from the analysis. In addition to the magnitude and type (against-the-rule, with-the-rule, and oblique) of astigmatism, we calculated the vector components (J0 , J45 ) and evaluated the association of these outcome measures with age. RESULTS: The magnitude of refractive astigmatism (RA) remained relatively stable [mean ± SD (-0.44 D ± 0.50)] until individuals reached the age of 50, thereafter increasing in average magnitude by approximately 1.00 D for those subjects aged 90. In contrast, corneal astigmatism (CA) remained relatively stable from childhood until the age of 80 (-0.76 D ± 0.61). The prevalence of clinically significant RA (≥1.00 D) increased with age and was highest in those aged >70 years [55.1% (47.2-62.7%)]. Age was significantly associated with RA in adults [odds ratio (OR) = 1.04 per 1 year, p < 0.001]. A weaker relationship was observed between CA and age (OR = 1.007 per 1 year, p = 0.02). CONCLUSIONS: We have confirmed the previously documented association between RA and age. Our results indicate that most of the observed change occurs after the age of 50, providing a recommended cut-off for participants in genetic studies of this refractive condition.

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BACKGROUND: 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. DESIGN: Cross-sectional population-based study. PARTICIPANTS: One thousand three hundred forty-four subjects aged 18-22 years in the Western Australian Pregnancy Cohort (Raine) Study. METHODS: Standardized colour and ultraviolet autofluorescence photographs of the nasal and temporal conjunctiva were taken, and assessed for presence of pterygium and area of autofluorescence. Sun exposure and protective factors were assessed by structured questionnaire. MAIN OUTCOME MEASURES: Area of conjunctival ultraviolet autofluorescence in square millimetre (mm(2)) and presence of pterygium. RESULTS: Median total conjunctival autofluorescence was 44.2 mm(2) (interquartile range 20.2-69.8 mm(2)). Median conjunctival autofluorescence was higher in nasal than in temporal quadrants (23.8 mm(2) vs. 18.9 mm(2), P < 0.001), but did not differ according to age or gender. Higher body mass index was associated with lower levels of autofluorescence. Total autofluorescence increased with increasing time spent outdoors. Prevalence of pterygium was 1.2% (95% confidence interval 0.6-1.8%), and was associated with male gender (odds ratio 6.71, P = 0.012). Participants with pterygium had significantly more conjunctival autofluorescence than those without (median 73.4 mm(2) vs. 44.0 mm(2), P = 0.001). CONCLUSIONS: Conjunctival ultraviolet autofluorescence is associated with increased time spent outdoors, and increased prevalence of pterygium. The association of this biomarker with other ophthalmohelioses, including cataract, ocular surface squamous neoplasia and eyelid malignancy, has yet to be determined.

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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.

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