Age-related macular degeneration and mortality: the Melbourne Collaborative Cohort Study.

AimsTo assess associations between features of age-related macular degeneration (AMD) and mortality.MethodsA total of 21 129 participants from the Melbourne Collaborative Cohort Study aged 47-85 years (60% female) were assessed for AMD (2003-2007). Mortality data to December 31, 2012 were obtained through linkage with the National Death Index. Associations were assessed using Cox regression, adjusting for age, sex, smoking, region of birth, education, physical activity, diet and alcohol.ResultsLate AMD was identified in 122 (0.6%) participants, including those with choroidal neovascularisation (n=55, 0.3%), geographic atrophy (n=87, 0.4%) and reticular pseudodrusen (n=87, 0.4%). After a median follow-up period of 8.1 years, 1669 (8%) participants had died, including those from cardiovascular diseases (386), tobacco-related cancers (179), and neurodegenerative disease (157). There was evidence of an increased rate of all-cause mortality for those with choroidal neovascularisation (Hazard Ratio (HR) 1.71 95% CI 1.06-2.76) and geographic atrophy (HR 1.46 95% CI 0.99-2.16). Choroidal neovascularisation was also associated with an increased rate of cardiovascular mortality (HR 3.16 95% CI 1.62-6.15) and geographic atrophy was associated with an increased rate of death from tobacco-related cancer (HR 2.86 95% CI 1.15-7.09). Weak evidence was also present for an association between choroidal neovascularisation and death from neurodegenerative disease (HR 2.49 95% CI 0.79-7.85). Neither reticular pseudodrusen nor the earlier stages of AMD were associated with mortality.ConclusionsLate AMD is associated with an increased rate of all-cause mortality. Choroidal neovascularisation and geographic atrophy were associated with death from cardiovascular disease and tobacco-related cancer, respectively.

Characteristics of progression of early age-related macular degeneration: the cardiovascular health and age-related maculopathy study.

AIMS: To determine the risk of age-related macular degeneration (AMD) progression posed by the presence of each early AMD characteristic. METHODS: A prospective cohort study of 254 participants aged 50 years and older, all with early AMD features at their baseline visit followed for an average of 7 years. Stereoscopic colour fundus photographs were graded for early AMD features using the International Classification System. AMD status was stratified into six exclusive levels along a continuum of disease severity according to drusen type, pigmentary abnormalities, or late AMD. Progression was assessed according to three definitions: a change between or within a severity level, or by side by side grading. RESULTS: The progression rate of early AMD ranged between 3.4 and 4.67% per annum depending upon the definition used. In total, 15 (6%) cases progressed from early AMD to the late complication of AMD. After controlling for age and smoking, cases with soft indistinct drusen at baseline were at a greater risk of progressing from early to late AMD than were cases without this characteristic (OR=3.72, 95%CI 1.20-11.54; P=0.02). CONCLUSION: Our proposed definitions of AMD progression give rates that are consistent with current knowledge of progression and its determinants. Each early AMD characteristic conveys its own risk of progression to an eye, with soft indistinct drusen carrying the greater risk. An international consensus on what defines AMD progression would greatly help the research community when trying to assess the importance of new risk factors and the effectiveness of novel interventions.

Methods for detecting age-related maculopathy: a comparison between photographic and clinical assessment.

PURPOSE: To examine the sensitivity, specificity and overall agreement between photographic and clinical assessment in detecting age-related maculopathy (ARM) features in the context of an epidemiological study, the Vitamin E, Cataract and Age-related Maculopathy Study (VECAT). METHODS: A total of 1204 volunteers aged between 55 and 80 years of age, who were enrolled in the VECAT Study, had both slit-lamp biomicroscopy examination and fundus photos taken as part of the baseline ophthalmic examination. The Nidek 3-DX fundus camera (Nidek, Gamagori, Japan) was used to produce paired, one-framed, coloured, 15 degrees stereoslides of the macular area at a fixed angle. An International Classification and Grading System for Age-related Maculopathy and Age-related Macular Degeneration was used to grade the stereoslides. Agreement in the detection of drusen, pigment abnormalities, and late stage ARM features was assessed using unweignted kappa statistic. Cases of disagreement were verified using clinical data records, grading documentation and the review of stereoslides. RESULTS: Macula status was available for 2386 eyes. For drusen of size < 63 microm, sensitivity was 47%, specificity was 68% with a kappa value of 0.20. For drusden > or = 125 microm, sensitivity and specificity were > or =81%. Kappa values ranged from 0.56 to 0.71. Levels of agreement for pigment abnormalities and late ARM were in the substantial range (i.e. kappa values from 0.70 to 1.00). CONCLUSIONS: Slit-lamp biomicroscopy was found to be comparable to photograding (using the Nidek 3-DX fundus camera) for detecting features pertaining to ARM. However, given the objectivity and permanency of stereoslides, photograding is still the more reliable and the preferred system of assessing ARM in the context of an epidemiological study.

Digital cataract photography.

This study compares the cost effectiveness of two methods of grading cataract changes in the Australian population. The conventional film-based method has comparatively low set-up costs, but is more subjective in its assessment and more reliant on manpower, while the digital method has high set-up costs, but the results are more objective and available more quickly using fewer people. By a careful assessment of all the costs involved it is possible to estimate how many participants need to be recruited to a study in order to make the digital method cost effective.

The VECAT study: methodology and statistical power for measurement of age-related macular features. Vitamin E, Cataract, and Age-related Maculopathy Study.

PURPOSES: (1) To develop the methodology for the grading of macular one-frame stereoslides and to assess the reliability of the system. (2) To determine the prevalence of soft drusen (> 63 microm) and pigment abnormalities synonymous with age-related maculopathy (ARM) at baseline, in a clinical trial of volunteers aged between 55 and 80 years of age. (3) To ascertain the power of the study to detect the 4-year incidence and progression of ARM in vitamin E versus placebo treated participants, given the baseline prevalence. METHODS: The 1204 participants enrolled in the Vitamin E, Cataract, and Age-related Maculopathy Study (VECAT) had colour stereoslides of their fundus taken using the Nidek 3-DX mydriatic fundus camera. The stereoslides were graded by two masked graders according to the "International Classification System for ARM and AMD". Assessment of inter- and intra-observer reliability was carried out on a regular basis on 15% of randomly selected slides. Anticipated rates of incidence and progression were based on results reported by the Beaver Dam Eye Study and the Chesapeake Bay Waterman Study. Power estimations were determined using the "nQuery Advisor" software program. Analyses were carried out on the worse affected eye. RESULTS: Inter-observer reliability was moderate to substantial (Kappa 0.5-0.88) whilst intra-observer agreement was high (0.6-1.0). The prevalence of any soft drusen was 32%. Significant associations were found between soft large indistinct drusen, hypopigmentation, hyperpigmentation and age (p = 0.0001, 0.024 and 0.0001, respectively). The study has at least 87% power to detect an odds ratio equal to two for the progression of soft distinct, soft indistinct, hyperpigmentation and hypopigmentation. CONCLUSIONS: The VECAT study methodology appears to be highly reliable and to have sufficient power to detect the differences in the four-year progression of soft distinct and indistinct drusen and pigment abnormalities between the treatment groups.

New software for lens retro-illumination digital image analysis.

PURPOSE: To describe functions of new software for cataract assessment and compare its validity with that of the Nidek EAS-1000 software (Nidek, Japan). METHODS: A new Microsoft Windows 3.1/95 (Microsoft, USA) compliant software, Retroillumination Image Analysis (RIA), has been developed. The cataract reading is based on the contrasts in illumination between the opaque and transparent areas of the lens. Image loading, pupil detection and image analyses are automated. Differentiation between the different cataract types (cortical/posterior subscapsular) and other opacities is possible. RESULTS: The program was tested on 233 Nidek EAS-1000 images. In all, 148 eyes had clear media or cortical cuneiform cataract, 37 also had confounding opacities and 48 had no confounding opacities but pupils were unevenly illuminated. The results of analysis with both Nidek EAS-1000 and RIA software were compared against clinical Wilmer grading. The correlation of cortical opacity size in Nidek EAS-1000 3.01c and RIA software, respectively, were 0.50* and 0.57* for whole data set, 0.54* and 0.55* for subgroup with no confounders or artefacts, 0.54* and 0.66* for subgroup with artefacts, 0.27 (P < 0.105) and 0.65* for subgroup with confounders (*P < 0.001). CONCLUSION: The RIA software significantly improves the accuracy of cataract measurement in lens images with uneven pupil illumination or confounding opacities. Automation of (i) image loading, (ii) pupil detection and (iii) defining of the opacity area increases the efficiency of digital eye photography, eliminates human errors and speeds assessment.

Cost-effectiveness of digital cataract assessment.

PURPOSE: The aim of this study was to compare costs of digital photograph grading with that of film-based, human grading of the lens in epidemiological studies involving cataract assessment. METHODS: Cost-effectiveness was measured by establishing the number of participants with ungradeable images and incorporating these lost data into the overall cost per participant for each study. RESULTS: The digital grading system cost was A$105000 with operating costs of $2.81 per participant, with 99.4% effectiveness. The film-based, human grading set-up costs were $43000 with operating costs of $18.49 per participant and 90% effectiveness. After examining 3500 people the use of the digital equipment becomes cost-beneficial. CONCLUSIONS: The high costs of setting up a digital cataract grading system are offset by the low running costs, less ungradeable images and greater accuracy over the duration of a large scale ophthalmic epidemiological study.

The role of past intake of vitamin E in early cataract changes.

PURPOSE: We examined the association between prior supplementation of vitamin E and early cataract changes in volunteers currently enrolled in the cross-sectional VECAT study. The Vitamin E and Cataract Prevention Study (VECAT) is a clinical trial currently in progress, designed to assess the affect of vitamin E supplementation on the development and progression of cataract and age-related macular degeneration. METHODS: A history of vitamin E supplementation was ascertained through a self-administered questionnaire that was mailed to each of the 1,111 participants who were enrolled at the time in the prospective VECAT Study. RESULTS: With a 99% response rate, we found that 26% of participants reported prior supplementation of vitamin E. Only 8.8% of these participants took supplementation greater than the recommended daily intake (RDI) of 10 mg/day. Of these 26%, 57% took supplementation in the form of multivitamins as opposed to a vitamin E supplement on its own. The range of supplement intake ranged from as little as 0.1 mg/day to a maximum of 55 mg/day. A statistically significant association was found between prior supplementation and the absence of cortical opacity (OR = 0.47, 95%CI = 0.28-0.83), after adjusting for age. The levels of nuclear opacity (NO) were not statistically different between those who reported intake and those with no prior vitamin E supplementation. CONCLUSION: Prior vitamin E supplementation may protect VECAT participants from developing at least early cortical cataracts. No apparent protective role in terms of nuclear opacities and nuclear color was found regardless of the level, regularity or duration of intake.

Variability in digital assessment of cortical and posterior subcapsular cataract.

To identify validity of the standardised Nidek EAS-1000 retroillumination image analysis, images of 450 consecutive patients were analysed for the standard 6.5 mm and for the maximal pupil size. The software allows for separation of cortical and posterior subcapsular opacities and defines threshold for cataract automatically at 12% below the brightest point of the histogram of pixel luminescence. The results were compared with clinical Wilmer cataract grading. Correlation between clinical and digital assessment was 0.48* for cortical opacities in maximal pupil size, 0. 47* in 6.5 mm pupil size analyses, and 0.71* for posterior subcapsular opacities (*p < 0.001). In 24.6% of maximal pupil size analyses and in 11.7% of standard pupil size analyses standardisation revealed confounding features, such as other opacities of media, refractive shadows etc., that masqueraded as cataract and interfered with the cortical opacity measurements. Automatic standardized analysis has reduced many sources of observer variation (level of illumination, pupil size and threshold adjustment), but the revealed range of confounding opacities and artifacts still requires observer interpretation.

Comparison of clinical and digital assessment of nuclear optical density.

To compare the standardised Nidek EAS-1000 densitometric analysis of the lens with clinical assessment of the nucleus at an early stage of cataract development, 1,200 eyes of 1,204 participants of the VECAT study were assessed at the baseline using both subjective and objective lens grading. Standardisation of the automatic slit image analysis was achieved using a custom-designed EAS-1000 Software version 3.01c. Among 6 measurements of nuclear optical density, the mean pixel luminescence of integrated anterior nuclear density correlated best with clinical assessment (R = 0.662, p < 0.001). Variance components that interfere with the assessment are defined.

Baseline ophthalmic findings in the vitamin E, cataract and age-related maculopathy (VECAT) study.

PURPOSE: To describe the methodology of eye examination and the baseline eye characteristics of the Vitamin E, Cataract and Age-Related Maculopathy (VECAT) study participants. METHODS: A sample of volunteers from an urban area of Melbourne, Australia, were recruited to participate in a randomized, controlled trial investigating the effect of vitamin E on the development of cataract and age-related maculopathy Standardized eye examinations involved clinical assessment, which included Wilmer grading of the lens, digital photography of the lens with Nidek EAS-1000 lens camera and stereo photography of the macular area with the Nidek 3-DX fundus camera. All cases of ophthalmic findings were determined on the basis of pathology in the worse eye. RESULTS: Most eyes were free from abnormalities. The most frequent findings were cataract and age-related macular changes. Nuclear cataract (nuclear opacity grade >2) was present in 4.5%, cortical cataract (cortical opacity grade >2) in 14.3% and posterior subcapsular cataract in 3.0% of participants; in addition, coronary cataract was observed in 13.6%. Soft drusen larger than 125 pm were found in 11.4%, retinal pigment epithelium changes in 9.5%, epiretinal membrane in 6.6% and age-related macular degeneration in 0.5% of participants. SUMMARY: Due to the selection criteria, the majority of participants had clear or minor lens changes and/or minor retinal age-related changes. Precise instrumental documentation will allow an accurate assessment of the incidence and dynamics of these changes throughout 4 years of observation.

Reproducibility of automatic standard digital analysis of lens opacities.

PURPOSE: This study was designed to assess the repeatability of the standard analysis of images taken with the Nidek EAS-1000 anterior segment analysis system (Nidek Co. Ltd, Japan). METHODS: Participants in a large clinical trial (the vitamin E, cataract and age-related maculopathy study) were asked to undergo two independent examinations to assess the repeatability of primary outcome measures. After pupil dilatation to at least 6.5 mm, 104 eyes were photographed using the retro-illumination method and the slit-beam method. RESULTS: Intra-class correlation coefficients were: slit images, R = 0.982; retro-illumination images, R = 0.978. CONCLUSION: Repeatability of measurement of lens opacity from EAS-1000 images using automated standard analysis was high.

[Outcomes of circular tunnel keratoplasty]. / Iskhody tsirkuliarnoi tonnel'noi keratoplastiki.

A new refraction operation for the correction of medium and high myopia, circulatory tunnel keratoplasty, has been theoretically validated, developed, experimentally tested, and tried in clinic. Experiments included 8 tested, in isolated cadaveric eyes and 72 surgeries on 39 rabbits. Experiments helped develop surgical equipment and technique. A relationship between the refraction effect and the diameter of the circulatory tunnel and implant thickness has been revealed. Time course of the refraction effect has been followed up for up to 2 years. The refraction diminished from 4.0 to 11.0 diopters. Thirty eyes of 21 patients with stable myopia of 6.0 to 22.0 diopters were operated on with the resultant refraction of 6.0 to 14.0 diopters. The results have confirmed the relationship between the refraction effect of surgery and the implant thickness. The authors claim that circulatory tunnel keratoplasty is an effective method for the correction of medium and high myopia and recommend it for clinical application.