Why bilateral medial rectus recession fails? Factors associated with early repeated surgery.

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.

Expression QTL analysis of glaucoma endophenotypes in the Norfolk Island isolate provides evidence that immune-related genes are associated with optic disc size.

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.

Effect of a punctal plug on ocular surface disease in patients using topical prostaglandin analogues: a randomized controlled trial.

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.

Genome-wide linkage and association analysis of primary open-angle glaucoma endophenotypes in the Norfolk Island isolate.

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.

Nd:YAG laser vitreolysis versus pars plana vitrectomy for vitreous floaters.

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.

Hydration, fluid regulation and the eye: in health and disease.

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.

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

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.

Incidence and predictors of glaucoma following surgery for congenital cataract in the first year of life in Victoria, Australia.

AIM: To determine the incidence and predictors of glaucoma following surgery for congenital and infantile cataract in an Australian population. DESIGN: Retrospective cohort study. PARTICIPANTS: Infants (<12 months) having had lens extraction between January 1992 and May 2006, from two tertiary referral centres. METHODS: Children with uveitis, anterior segment dysgenesis, aniridia, retinopathy of prematurity, and lens subluxation were excluded. Potential predictors of incident glaucoma were examined using Cox proportional hazards regression with adjustment for clustering between eyes. MAIN OUTCOME MEASURES: Incidence and predictors of secondary glaucoma. RESULTS: One hundred and forty-seven eyes of 101 patients (46 bilateral cataract; 55 unilateral cataract) were included, with median follow-up of 9.9 years (range 1.2-18.9 years). Cumulative incidence of glaucoma was 32.0% for eyes (n = 47) and 30.7% (n = 31) for subjects. Incidence was higher in children with bilateral cataract (38.9 vs. 17.1%, p = 0.004). There were 3.9 cases of glaucoma per 100 person years of follow-up, the incidence rate being highest for surgery performed in the first month of life. Children with glaucoma had longer median follow-up (11.8 vs. 9.3 years, p = 0.005). Risk of glaucoma decreased with increasing months of age at operation: hazard ratio 0.79, 95% confidence interval 0.69-0.91, p = 0.001. Median visual acuity was worse in children with unilateral cataract (p < 0.001). CONCLUSIONS: We identified an increased risk of glaucoma when cataract surgery was performed in younger infants, and in those with bilateral cataract. As glaucoma may develop over a decade following lens extraction, life-long surveillance is needed to prevent glaucoma-associated vision loss.

The association between time spent outdoors and myopia in children and adolescents: a systematic review and meta-analysis.

OBJECTIVE: To summarize relevant evidence investigating the association between time spent outdoors and myopia in children and adolescents (up to 20 years). DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Results from 7 cross-sectional studies were pooled in a meta-analysis. A further 16 studies (8 cross-sectional not meeting criteria for meta-analysis; 7 prospective cohort studies; 1 randomized, controlled trial [RCT]) were reported in the systematic review. METHODS: The literature search included 4 databases (Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials [CENTRAL]), and reference lists of retrieved studies. Estimates of association were pooled using random effects meta-analysis. We summarized data examining the association between time spent outdoors and prevalent myopia, incident myopia, and myopic progression. MAIN OUTCOME MEASURES: Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for myopia for each additional hour spent outdoors per week from a meta-analysis. RESULTS: The pooled OR for myopia indicated a 2% reduced odds of myopia per additional hour of time spent outdoors per week, after adjustment for covariates (OR, 0.981; 95% CI, 0.973-0.990; P<0.001; I(2), 44.3%). This is equivalent to an OR of 0.87 for an additional hour of time spent outdoors each day. Three prospective cohort studies provided estimates of risk of incident myopia according to time spent outdoors, adjusted for possible confounders, although estimates could not be pooled, and the quality of studies and length of follow-up times varied. Three studies (2 prospective cohort and 1 RCT) investigated time spent outdoors and myopic progression and found increasing time spent outdoors significantly reduced myopic progression. CONCLUSIONS: The overall findings indicate that increasing time spent outdoors may be a simple strategy by which to reduce the risk of developing myopia and its progression in children and adolescents. Therefore, further RCTs are warranted to investigate the efficacy of increasing time outdoors as a possible intervention to prevent myopia and its progression.

Outcomes of manual small-incision cataract surgery using standard 22 dioptre intraocular lenses at Nkhoma Eye Hospital, Malawi.

The aim of this study was to investigate the outcomes of sutureless, manual small-incision cataract surgery (SICS) in rural sub-Saharan Africa using standard intraocular lenses (IOLs). In order to assess the quality of surgery, we prospectively evaluated the visual outcomes of 1455 consecutive cataract operations performed in 2006 in patients ≥40 years at Nkhoma Eye Hospital, Malawi. All operations used standard 22-dioptre IOLs without pre-operative biometry. Outcomes were categorised according to the World Health Organization criteria, and causes of a poor outcome were recorded. Mean age of patients was 71.5 ± 9.5 years, and 53 % were female. Pre-operatively, 64 % of eyes had a visual acuity (VA) <6/60, and 41.3 % of eyes were blind (VA < 3/60). Without correction (uncorrected VA), nearly eighty percent (78.7 %) achieved a 'good' outcome (VA 6/6-6/18), 19.8 % were 'borderline' (VA < 6/18-6/60), and 1.5 % had a poor (VA < 6/60) outcome. With pinhole-correction, the proportion of good outcomes increased to 89.4 %, and poor outcomes decreased to 0.9 %. Poor outcomes were most commonly due to ocular co-morbidities (54.5 %) and refractive error (36.4 %). Older age and pre-operative blindness were strongly associated with borderline or poor visual outcomes. The most common surgical complication was posterior capsule tear (without vitreous loss). In a rural African environment, using standard IOL power plus SICS can lead to a high proportion of good outcomes and a low frequency of surgical complications. A comparative study is required to determine if any additional benefit in visual outcomes can be gained by the addition of biometry.

The Norfolk Island Eye Study (NIES): rationale, methodology and distribution of ocular biometry (biometry of the bounty).

AIM: To describe the recruitment, ophthalmic examination methods and distribution of ocular biometry of participants in the Norfolk Island Eye Study, who were individuals descended from the English Bounty mutineers and their Polynesian wives. METHODS: All 1,275 permanent residents of Norfolk Island aged over 15 years were invited to participate, including 602 individuals involved in a 2001 cardiovascular disease study. Participants completed a detailed questionnaire and underwent a comprehensive eye assessment including stereo disc and retinal photography, ocular coherence topography and conjunctival autofluorescence assessment. Additionally, blood or saliva was taken for DNA testing. RESULTS: 781 participants aged over 15 years were seen (54% female), comprising 61% of the permanent Island population. 343 people (43.9%) could trace their family history to the Pitcairn Islanders (Norfolk Island Pitcairn Pedigree). Mean anterior chamber depth was 3.32mm, mean axial length (AL) was 23.5mm, and mean central corneal thickness was 546 microns. There were no statistically significant differences in these characteristics between persons with and without Pitcairn Island ancestry. Mean intra-ocular pressure was lower in people with Pitcairn Island ancestry: 15.89mmHg compared to those without Pitcairn Island ancestry 16.49mmHg (P = .007). The mean keratometry value was lower in people with Pitcairn Island ancestry (43.22 vs. 43.52, P = .007). The corneas were flatter in people of Pitcairn ancestry but there was no corresponding difference in AL or refraction. CONCLUSION: Our study population is highly representative of the permanent population of Norfolk Island. Ocular biometry was similar to that of other white populations. Heritability estimates, linkage analysis and genome-wide studies will further elucidate the genetic determinants of chronic ocular diseases in this genetic isolate.

Prevalence and predictors of refractive error in a genetically isolated population: the Norfolk Island Eye Study.

BACKGROUND: We aimed to determine the prevalence and associations of refractive error on Norfolk Island. DESIGN: Population-based study on Norfolk Island, South Pacific. PARTICIPANTS: All permanent residents on Norfolk Island aged ≥ 15 years were invited to participate. METHODS: Patients underwent non-cycloplegic autorefraction, slit-lamp biomicroscope examination and biometry assessment. Only phakic eyes were analysed. MAIN OUTCOME MEASURES: Prevalence and multivariate associations of refractive error and myopia. RESULTS: There were 677 people (645 right phakic eyes, 648 left phakic eyes) aged ≥ 15 years were included in this study. Mean age of participants was 51.1 (standard deviation 15.7; range 15-81). Three hundred and seventy-six people (55.5%) were female. Adjusted to the 2006 Norfolk Island population, prevalence estimates of refractive error were as follows: myopia (mean spherical equivalent ≥ -1.0 D) 10.1%, hypermetropia (mean spherical equivalent ≥ 1.0 D) 36.6%, and astigmatism 17.7%. Significant independent predictors of myopia in the multivariate model were lower age (P < 0.001), longer axial length (P < 0.001), shallower anterior chamber depth (P = 0.031) and increased corneal curvature (P < 0.001). Significant independent predictors of refractive error were increasing age (P < 0.001), male gender (P = 0.009), Pitcairn ancestry (P = 0.041), cataract (P < 0.001), longer axial length (P < 0.001) and decreased corneal curvature (P < 0.001). CONCLUSIONS: The prevalence of myopia on Norfolk Island is lower than on mainland Australia, and the Norfolk Island population demonstrates ethnic differences in the prevalence estimates. Given the significant associations between refractive error and several ocular biometry characteristics, Norfolk Island may be a useful population in which to find the genetic basis of refractive error.

Tumor volume in radical prostatectomy specimens assessed by digital image analysis software correlates with other prognostic factors.

PURPOSE: Digital image analysis software to review histopathology specimens is advancing uropathology by objectivity and reproducibility. Subjective pathologist assessed prostate tumor volume calculations correlate with known prognostic factors at radical prostatectomy. We ascertained whether image analysis software calculations of prostate tumor volume correlate with such prognostic factors, particularly positive surgical margins. MATERIALS AND METHODS: Prostate tumor volume was calculated using digital image analysis software in 851 sequential radical prostatectomy specimens. Results were correlated with clinicopathological data by logistic regression. RESULTS: Median prostate tumor volume was 2.2 cc (IQR 0.9-3.8). Median peripheral and transition zone tumor volume was 1.9 and 0.6 cc, respectively. Transition zone tumors were noted in 236 specimens (27.8%) and positive surgical margins occurred in 244 (28.7%). Tumors with extensive positive surgical margins had larger image analysis software assessed prostate tumor volume (p = 0.029) and peripheral zone volume (p = 0.007) than those with only focal positive surgical margins. On univariate analysis positive surgical margin tumors were larger and had seminal vesicle invasion, extraprostatic extension, perineural invasion and higher preoperative prostate specific antigen than those without positive surgical margins (each p <0.001). A linear relationship existed between image analysis software determined prostate tumor volume, and increasing tumor stage, Gleason score and prostate specific antigen (p for trend <0.001). On multivariate analysis tumor volume and tumor volume as a percent of prostate volume predicted positive surgical margins. CONCLUSIONS: Prostate tumor volume determined objectively by image analysis software correlates with positive surgical margins, as do prognostic variables such as extraprostatic extension, seminal vesicle invasion, perineural invasion, peripheral zone volume and Gleason score greater than 7. Objective digital image analysis software assessment appears to be a valid form to determine prostate tumor volume at radical prostatectomy. It is a useful adjunct to other histopathological analyses.