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Background: To examine whether the clinical performance of predicting late age-related macular degeneration (AMD) development is improved through using multimodal imaging (MMI) compared to using colour fundus photography (CFP) alone, and how this compares with a basic prediction model using well-established AMD risk factors., Methods: Individuals with AMD in this study underwent MMI, including optical coherence tomography (OCT), fundus autofluorescence, near-infrared reflectance and CFP at baseline, and then at 6-monthly intervals for 3-years to determine MMI-defined late AMD development. Four retinal specialists independently assessed the likelihood that each eye at baseline would progress to MMI-defined late AMD over 3-years with CFP, and then with MMI. Predictive performance with CFP and MMI were compared to each other, and to a basic prediction model using age, presence of pigmentary abnormalities, and OCT-based drusen volume., Results: The predictive performance of the clinicians using CFP [AUC = 0.75; 95% confidence interval (CI) = 0.68-0.82] improved when using MMI (AUC = 0.79; 95% CI = 0.72-0.85; p = 0.034). However, a basic prediction model outperformed clinicians using either CFP or MMI (AUC = 0.85; 95% CI = 0.78-91; p ≤ 0.002)., Conclusions: Clinical performance for predicting late AMD development was improved by using MMI compared to CFP. However, a basic prediction model using well-established AMD risk factors outperformed retinal specialists, suggesting that such a model could further improve personalised counselling and monitoring of individuals with the early stages of AMD in clinical practice., (© 2024 The Author(s). Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Background: Nocturnal hypoxia is common, under-diagnosed and is found in the same demographic at risk of age-related macular degeneration (AMD). The objective of this study was to determine any association between nocturnal hypoxia and AMD, its severity, and the high-risk sub-phenotype of reticular pseudodrusen (RPD)., Methods: This cross-sectional study included participants aged ≥50 years with AMD, or normal controls, exclusive of those on treatment for obstructive sleep apnoea. All participants had at home, overnight (up to 3 nights) pulse oximetry recordings and multimodal imaging to classify AMD. Classification of Obstructive Sleep Apnea (OSA) was determined based on oxygen desaturation index [ODI] with mild having values of 5-15 and moderate-to-severe >15., Results: A total of 225 participants were included with 76% having AMD, of which 42% had coexistent RPD. Of the AMD participants, 53% had early/intermediate AMD, 30% had geographic atrophy (GA) and 17% had neovascular AMD (nAMD). Overall, mild or moderate-to-severe OSAwas not associated with an increased odds of having AMD nor AMD with RPD (p ≥ 0.180). However, moderate-to-severe OSA was associated with increased odds of having nAMD (odds ratio = 6.35; 95% confidence interval = 1.18 to 34.28; p = 0.032), but not early/intermediate AMD or GA, compared to controls (p ≥ 0.130). Mild OSA was not associated with differences in odds of having AMD of any severity (p ≥ 0.277)., Conclusions: There was an association between nocturnal hypoxia as measured by the ODI and nAMD. Hence, nocturnal hypoxia may be an under-appreciated important modifiable risk factor for nAMD., (© 2024 The Author(s). Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Background: To examine the association between large choroidal signal hypertransmission ≥250 μm (LHyperT) on optical coherence tomography (OCT) with the risk of developing geographic atrophy (GA) and compare this risk with those associated with nascent geographic atrophy (nGA)., Methods: Two hundred and eighty eyes from 140 participants with bilateral large drusen and without late age-related macular degeneration (AMD) or nGA at baseline underwent OCT imaging and colour fundus photography (CFP) at 6-monthly intervals up to 5 years. OCT scans were graded for the presence of LHyperT and nGA, and CFPs were graded for the presence of GA., Results: The five-year incidence of LHyperT and nGA were 37% and 27% respectively (p = 0.003), and the two-year probability of their progression to GA were 17% and 40%, respectively (p = 0.002). LHyperT and nGA explained 81% and 91% of the variance in the time to develop GA, respectively (p = 0.032), and they were both associated with a significantly higher rate of GA development compared to eyes without these lesions (adjusted hazard ratio = 110.8 and 183.2, respectively; p < 0.001 for both)., Conclusions: LHyperT and nGA were both high-risk features for GA development, but the latter showed a higher rate of GA progression and explained a significantly greater proportion of the variance in the time to develop GA. As such, nGA may be a more robust surrogate endpoint than LHyperT for the conventional clinical endpoint of CFP-defined GA for intervention trials in the early stages of AMD., (© 2024 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Background: We aimed to describe the self-reported level of eyesight amongst a cohort of relatively healthy older Australian adults, and to investigate associations between poorer self-rated eyesight and demographic, health, and functional characteristics METHODS: The ASPirin in Reducing Events in the Elderly (ASPREE) Longitudinal Study of Older Persons (ALSOP) study was embedded in a multisite trial which recruited independently living Australians from general practices (2010-2014). Self-rated eyesight was recorded on a paper-based questionnaire as Excellent, Good, Fair, Poor, Very poor, or Completely blind at the baseline study wave RESULTS: Data from 14 592 participants (aged 70-95 years, 54.61% female) were included in this cross-sectional analysis. Eighty percent of participants reported excellent or good eyesight (n = 11 677). People with complete blindness were precluded from enrolling but 299 participants (2.0%) reported poor or very poor eyesight, and 2616 rated their eyesight as fair (17.9%). Lower levels of eyesight were associated with being older, female, fewer years of formal education, a primary language other than English, smoking, and self-reported macular degeneration, glaucoma, retinopathy, cataracts, and hearing problems (each p ≤ 0.021). People with lower levels of eyesight had a higher number of falls, frailty characteristics, and depressive symptoms, and lower mental and physical health functioning scores (each p < 0.001) CONCLUSIONS: Whilst most of these healthy older Australians reported good or excellent eyesight, a notable minority reported poor or very poor eyesight, and this was associated with a range of poorer health measures. These findings support the need for additional resources to prevent vision loss and associated sequelae., (© 2023 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Background: Subthreshold nanosecond laser (SNL) treatment has been studied as a potential intervention in intermediate age-related macular degeneration (iAMD). This study investigated the effect of 100 SNL treatment spots on retinal structure and function., Methods: A prospective single-arm interventional pilot study. SNL treatment was delivered as 100 spots around the retinal vascular arcades of the study eye (worst visual acuity) in a single session in subjects with iAMD. Multimodal retinal imaging and dark-adapted chromatic perimetry were performed at baseline and at 0.5, 3, 6 and 12 months post treatment. Post treatment changes in best corrected visual acuity (BCVA), retinal thickness, relative ellipsoid zone reflectivity (rEZR) and rod-mediated functional parameters were compared to baseline., Results: Twenty-one subjects with iAMD were recruited. SNL treatment was associated with an increase in retinal thickness (p = 0.008) and decrease in rEZR (p < 0.001) at 2 weeks post laser. Recovery of retinal thickness and rEZR was observed at the 3-month post laser visit. A gradual improvement in BCVA was observed after laser treatment. The mean change in BCVA between baseline and 12-month visit was +1.9 ± 3.3 letters for the SNL treated eyes, compared to -0.4 ± 3.0 letters for the fellow eyes (p = 0.027). Rod-mediated function improved at 3 months post laser (p < 0.001) and returned to the baseline levels at 12 months post treatment., Conclusions: A single treatment with 100 SNL spots causes a short-term change in retinal structure and improvement in retinal function that are apparent at 3 months post treatment., (© 2021 Royal Australian and New Zealand College of Ophthalmologists.)

Importance: The effect of sub-threshold nano-second laser (SNL) treatment on retinal function remains unknown., Background: SNL treatment has been studied as a potential intervention in intermediate age-related macular degeneration (iAMD). This study investigated the longitudinal effect of SNL treatment on retinal function., Design: This was a sub-study of the LEAD trial; a 36-month, multi-centre, randomized and sham-controlled trial., Participants: Subjects with iAMD., Methods: Eligible participants were assigned randomly to receive SNL or sham treatment to the study eye at 6-monthly visits. Multi-focal electro-retinography (mfERG) was performed at each study visit from a study site. The mfERG responses were grouped into three regions (central, middle and outer rings) and compared between the SNL and sham group., Main Outcome Measures: mfERG P1 response amplitude and implicit time., Results: Data were collected from 50 subjects (26 in the SNL group, 24 in the sham group). At baseline, the P1 amplitudes of both the study eyes and the fellow eyes were similar between the groups at all rings. In the sham group, the P1 amplitude gradually decreased over time (P < .05). In the SNL group, there was an improvement in P1 amplitude which became statistically significant at the 36-month visit, detected in both the treated and fellow eyes at the central (P = .005) and middle ring (P = .007) but not at the outer ring (P = .070). No difference in P1 implicit time detected between the groups (P > .05)., Conclusions and Relevance: SNL treatment improved electro-physiological function. mfERG could be useful for monitoring AMD progression and evaluating the efficacy of SNL treatment., (© 2020 Royal Australian and New Zealand College of Ophthalmologists.)

Importance: Reticular pseudodrusen (RPD) is strongly associated with late age-related macular degeneration (AMD) but their aetiology remains unknown. RPD have been associated with reduced choroidal thickness (ChT) but most studies are limited by small sample size and varying severity of AMD., Background: To investigate the relationship between choroidal thickness and RPD in eyes with intermediate AMD (iAMD), controlling for variables known to influence ChT., Design: Retrospective cohort study., Participants: Participants were recruited from Centre for Eye Research Australia., Methods: Colour fundus photographs, fundus auto fluorescence, near-infrared and spectral-domain ocular coherence tomography (OCT) were graded for RPD. ChT was measured from enhanced-depth imaging OCT scans at the centre of fovea, 1500 and 3000 μm nasal, temporal, superior and inferior from centre of fovea., Main Outcome Measures: ChT between RPD and non-RPD group., Results: A total of 297 eyes from 152 subjects were included. A total of 84 (28%) had RPD and were older than non-RPD group (75.1 ± 5.4 years and 68.7 ± 6.9 years, respectively; P < 0.001). In unadjusted analysis, the RPD group was significantly associated with thinner choroids across all measured locations (P ≤ 0.022). After adjustment for variables, the presence of RPD was no longer associated with ChT (P ≥ 0.132 for all locations) but age (P < 0.001) and refractive error (P = 0.002) remained significantly associated with ChT., Conclusions and Relevance: Age and refractive error, rather than RPD, was significantly associated with reduced ChT in eyes with iAMD. Choroidal insufficiency may be a less important variable in RPD aetiology than previously considered., (© 2017 Royal Australian and New Zealand College of Ophthalmologists.)

Importance: Identifying variables that influence presenting visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD) is important because it is a strong predictor of long-term outcomes., Background: To assess the clinical and social characteristics associated with low presenting VA in nAMD patients., Design: The present study is a cross-sectional analysis from a prospective, observational database., Participants: We identified 3242 treatment-naïve patients from 54 Australian practices in the Fight Retinal Blindness! registry., Methods: Age, gender, ethnicity and VA were recorded at the baseline visit. Socio-economic status was determined using the Australian Bureau of Statistics socio-economic indexes for areas., Main Outcome Measures: Association between clinical and socio-economic characteristics with presenting VA was identified., Results: Poor VA (≤35 letters) in the presenting eye was associated with older age (adjusted odds ratio [AOR]: 1.33 for patients aged ≥80 years vs. <80 years [95% confidence interval, CI: 1.04, 1.71]), treatment at a public practice (AOR: 1.91 for public vs. private practices [95% CI: 1.46, 2.50]) and intermediate (36-69 letters) VA in the fellow eye (AOR: 0.67 [95% CI: 0.47, 0.95] and 0.64 [95% CI: 0.48, 0.85] for poor [≤35 letters] and good [≥70 letters] VA vs. intermediate VA in the fellow eye). Gender, ethnicity and socio-economic status were not independently associated with VA at presentation., Conclusions and Relevance: Poor presenting vision is detrimental to the long-term outcomes of nAMD. Poor presentation of nAMD in Australia may not be related to socio-economic circumstances, but due to systems of care. Further research is warranted to determine why patients at public practices present with worse vision compared with private practices in Australia., (© 2017 Royal Australian and New Zealand College of Ophthalmologists.)

Background: Late neovascular age-related macular degeneration (nvAMD) is very common and causes irreversible severe visual loss unless treated swiftly with vascular endothelial growth factor (VEGF) inhibitors. Although publicly subsidized access to treatment may be inequitable, which is why we assessed treatment provision across Australia., Design: Secondary analysis of Australian data., Participants: All Pharmaceutical Benefits Scheme (including Repatriation PBS) beneficiaries., Methods: Treatment and incidence data were obtained from Medicare Australia, the Royal Australian and New Zealand College of Ophthalmologists, Optometry Australia, the Blue Mountains Eye Study and the Australian Bureau of Statistics. Data were mapped using geographical information software, and factors associated with treatment provision were assessed using multiple linear regression models., Main Outcome Measure: Unmet need (%) for anti-VEGF treatment for nvAMD., Results: On average, we estimated 7316 incident cases of nvAMD not to be treated per year from 2010 to 2014 (50.1% of total). Number of ophthalmologists and optometrists (per 1000, β = -0.024; 95% confidence interval [CI] -0.041, -0.007) and being located in remote regions (β = 0.186; 95% CI 0.110, 0.262) were associated with percentage of untreated cases. A higher proportion of the population speaking a language other than English at home was associated in univariate analyses only (β = 0.0015; 95% CI -0.0004, 0.0027; P = 0.007)., Conclusion: A large proportion of incident nvAMD is not treated with anti-VEGF. Not receiving treatment is more likely in regional or remote areas and areas with fewer service providers. Not speaking English at home may further limit access. Service delivery models for more equitable service provision are needed., (© 2016 Royal Australian and New Zealand College of Ophthalmologists.)

Emergence of the high-resolution optical coherence tomography has allowed better delineation of retinal layers, and many of the anatomical correlations of these layers have now been agreed upon. However, some anatomical correlates still remain contentious, such as the second hyper-reflective band, which is now termed ellipsoid zone. Despite the lack of consensus of the actual origin of the ellipsoid zone, there has been much interest in evaluating its integrity and intensity in different disease processes. This review paper aims to provide an overview of the ellipsoid zone and its clinical and research applications., (© 2015 Royal Australian and New Zealand College of Ophthalmologists.)

Background: A novel, ultra-low energy nanosecond laser (retinal rejuvenation therapy) has been developed with the aim to slow progression of early age-related macular degeneration (AMD). The safety, changes in fundus characteristics and macular function in a cohort of participants with bilateral intermediate AMD are reported., Design: Prospective non-randomised, pilot intervention study., Participants or Samples: Subjects with bilateral intermediate AMD (n = 50, aged 50-75 years)., Methods: Ultra-low energy laser pulses applied in 12 spots around the macula of one eye (0.15-0.45 mJ), using 400 μm diameter spot, 3 nanosecond pulse length, 532 nm wavelength and energy titrated to each patient., Main Outcome Measures: Best corrected visual acuity, drusen area and macular sensitivity (flicker perimetry) at baseline and at 3, 6 and 12 months post-laser., Results: Treatment was painless with no clinically visible lesions. No participant developed choroidal neovascularization, while two with thin central retinal thickness at baseline developed atrophy at 12-month follow up. Drusen area was reduced in 44% of treated eyes and 22% of untreated fellow eyes, with changes in drusen and function not being coincident. Improvement in flicker threshold within the central 3° was observed in both the treated and untreated fellow eyes at 3 months post-laser. Of the 11 eyes at greatest risk of progression (flicker defect >15 dB), seven improved sufficiently to be taken out of this high-risk category., Conclusions: A single unilateral application of nanosecond laser to the macula produced bilateral improvements in macula appearance and function. The nanosecond retinal rejuvenation therapy laser warrants ongoing evaluation as an early intervention for AMD., (© 2013 Royal Australian and New Zealand College of Ophthalmologists.)

Background: Little quantitative information exists regarding the effect that retinitis pigmentosa (RP) has on the choroid. The aim of this study was to determine choroidal thickness profiles in patients with RP., Design: Prospective., Participants: Forty-two RP and 22 control subjects participated in the study. RP patients had mild to severe disease, with a visual acuity range of logMAR 0.1 to no light perception., Methods: Images of the retina and choroid were obtained using the enhanced depth-imaging method and optical coherence tomography (OCT). Choroidal thickness measures were determined via manual segmentation of the OCT image., Main Outcome Measures: The thickness profiles of the normal and RP groups were compared. The associations between choroidal thickness, visual acuity and duration of RP were determined., Results: The choroid was thickest in the control eyes at the subfoveal location (336.60 ± 70.42 μm), and the thickness gradually decreased towards the peripheral retina (temporal 8° = 295.55 ± 60.52 μm; nasal 8° = 251.68 ± 49.93 μm). In RP, the mean thickness was also greater at the fovea (215.60 ± 94.91 μm) than the temporal (191.66 ± 72.42 μm) and nasal (149.91 ± 57.42 μm) retina, but all values were significantly lower than those of the controls (P ≤ 0.001). Subfoveal choroidal thickness was significantly correlated with visual acuity (r = -0.46, P < 0.001) and duration of disease (r = -0.4, P = 0.001)., Conclusions: Patients with RP have a thinner choroid than controls. Patients with poorer visual acuity or longer duration of symptoms tended to have thinner choroids. Knowledge of choroidal thickness profile in RP is important for the field of restorative vision research and the development of suprachoroidal retinal prostheses., (© 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.)

The last decade has produced pivotal change in our understanding of the molecular mechanisms underlying age-related macular degeneration (AMD), a leading cause of global blindness. In this time, the complement system has featured as a unifying theme for several elements of new evidence: initially, the discovery of complement proteins within drusen and subsequently, the association between AMD and mutations in various complement pathway genes, most notably complement factor H. Increasingly, a wealth of data are pointing towards a role for chronic local inflammation and complement activation in the patho-aetiology of AMD. These findings have paved the way for the exploration of a new paradigm of therapy in AMD management; targeting of specific molecular constituents in the complement pathway thus producing dampening or inhibition of the inflammatory response. Such an approach has the potential to intervene earlier in the disease process and ideally before vision is compromised. In this review we discuss the role of the complement system in AMD, novel therapies in preclinical evaluation and clinical trial, and whether these have a part to play in reducing the burden of disease., (© 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.)

Background: To describe the changes in retinal vascular calibre in response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration., Design: Prospective interventional case series., Participants: Treatment naïve patients with neovascular age-related macular degeneration were recruited over a 1-year period., Methods: Each patient received three monthly intravitreal injections according to a 'loading dose'. Retinal arteriolar and venular calibre was measured from digital fundus photographs and summarized as central retinal artery equivalent and central retinal vein equivalent at baseline and 3 months., Main Outcome Measure: Central retinal artery equivalent and central retinal vein equivalent changes from baseline to 3 months., Results: Seventy-four eyes of 71 patients had good quality images for grading vessel calibre at baseline and at 3 months in treated (study) eyes and 51 eyes of 51 patients had good quality images in fellow (control) eyes. Over 3 months, in study eyes treated with ranibizumab, there was a significant increase in central retinal vein equivalent over baseline (+6.20 µm, P = 0.005), but no significant change in central retinal artery equivalent (+0.86 µm, P = 0.55). In control eyes, there was no change in central retinal vein equivalent (-0.82 µm, P = 0.70) or central retinal artery equivalent (0.34 µm, P = 0.75)., Conclusion: Intravitreal ranibizumab has a significant vasodilational effect on retinal venular calibre in eyes treated for neovascular age-related macular degeneration. The reason for this change is unclear, but may relate to changes in blood flow or inflammatory changes within the retina., (© 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.)

It can be argued that age-related macular degeneration is one of the best characterized complex trait diseases. Extensive information related to genetic and environmental risk factors exists, and a number of different biological pathways are strongly implicated in its aetiology. Along with recent improvements in high throughput and relatively inexpensive genetic technologies, we are now in a position to consider developing a presymptomatic, personalized approach towards the assessment, management and treatment of this disease. We explore the applicability and challenges of this approach if it is to become commonplace for guiding treatment decisions for individuals with pre-existing disease or for those at high risk of developing it.

Background: To investigate if cataract surgery causes progression, from high-risk early age-related macular degeneration (AMD) to choroidal neovascularization (CNV), in the postoperative period., Methods: Randomized controlled trial. Patients, with visually significant cataract and fundus features of early AMD at high risk of progression to CNV, were randomized into two groups and were evaluated at baseline and 6 months. The study patients (n = 27) underwent immediate cataract surgery. The control group (n = 29) comprised patients who had cataract surgery deferred until after the 6-month visit. Assessment included visual acuity, quality of life (QoL) and fundus fluorescein angiography (FFA)., Results: Of 68 eligible eyes, 60 participated and 56 completed the study. Three referred eyes (3.2%) were ineligible on the basis of a pre-existing, unsuspected occult CNV that was detected by baseline FFA. All three cases had end-stage exudative AMD in the fellow eye. Of the study eyes in the immediate surgery arm (n = 27), one (3.7%) developed CNV compared with none (0/29) in the deferred arm (chi(2); P = 1.0) at 6 months. In the operated group, there was a 2.8-line improvement in logMAR visual acuity and 2.1-fold average gain in QoL at 6 months., Conclusions: No increased short-term risk of progression of AMD to CNV in high-risk fundi following uncomplicated phacoemulsification surgery was found. A low threshold for performing preoperative imaging in patients with AMD, especially in those with exudative AMD in the fellow eye, to exclude undetected CNV is recommended. Provided there is no CNV, there are distinct benefits of cataract surgery in people with early AMD.

Background: Photodynamic therapy with verteporfin for choroidal neovascularization (CNV) secondary to macular disease received an Australian government grant in 2002 to fund treatment for 3 years. Funding was restricted to subfoveal predominantly classic CNV where visual acuity was at least 6/60. Access to this funding was via review of angiograms by an expert panel, the Angiogram Review Panel (ARP), managed by the Royal Australian and New Zealand College of Ophthalmologists., Methods: De-identified data from the ARP were obtained for the period June 2002 to April 2005 inclusive and the panel's outcomes were analysed. Health Insurance Commission and Department of Veteran Affairs data for photodynamic therapy for the same interval were also retrieved., Results: A total of 7198 submissions to the ARP were received for 5867 individuals in this period. Overall 86.6% eyes submitted were accepted for initial funding (treatments 2-4). There was no change over time in the percentage rejected during this period. The first reviewer accepted 77.2%. And the second reviewer accepted a further 7.7%. An additional 1.6% were accepted on appeal. It was estimated that 29.2% of this initial cohort received five or more treatments., Conclusions: The ARP data indicate an incidence of subfoveal predominantly classic CNV secondary to macular disease in Australia of about 2000 eyes per annum. Only one quarter of patients received five or more treatments. The panel provided a unique opportunity to estimate the 'whole of nation' incidence of predominantly classic subfoveal CNV secondary to macular disease and thus provides a firm foundation upon which to plan public health spending as new treatments become available.

Cardiovascular disease and age-related macular degeneration (AMD) may share common risk factors in their causal pathways. Decades of research from the cardiovascular sciences on fats have led investigators to focus on specific types of fats rather than total fat as a whole. They have established that saturated and trans-unsaturated fats (trans fats) are damaging to cardiovascular health while polyunsaturated fats, particularly the marine omega 3 fatty acids appear protective. This has led to a number of studies investigating the associations of fat and AMD. Though the causal relationship between fats and AMD remain unproven, some studies suggest that an association may be present. To be able to understand and interpret the study results and their implications, an understanding of the fats in the diet is important. This review aims to give an overview of fatty acids, particularly the trans-unsaturated fatty acids, and the relevant food groups.

Aim: To investigate the relationship between iris colour, ethnic origin and the progression of age-related macular degeneration (AMD)., Methods: Participants were recruited from the population-based Melbourne Visual Impairment Project or the prospective, randomized, double-masked Vitamin E, Cataract and Age-Related Macular Degeneration study. From these two cohorts, 171 participants aged between 52 and 93 years who were identified as having early AMD features at their baseline examination (1992-1995) were followed for an average of 6.8 years (until 2001) to determine the progression rate of early AMD. The participants' iris colour was categorized as light, intermediate or dark. Ethnic origin was categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants' grandparents' country of birth., Results: In total, 53 (31%) of the 171 participants showed signs of AMD progression. Participants with light iris colour had twofold the risk of AMD progression of those with dark or intermediate iris colours, although the age-adjusted and multivariate-adjusted associations were not significant (both P = 0.13). Age-adjusted and multivariate comparisons of Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable but non-significant association with progression of AMD (P= 0.22 and P= 0.14, respectively)., Conclusion: Individuals with light iris colour or of Anglo-Saxon ethnic origin had a strong tendency to greater progression of AMD. A larger sample is required to confirm these clinically important, but statistically non-significant, associations.

Purpose: To review the 12-month results of the first 136 eyes treated with photodynamic therapy (PDT) with verteporfin at a single institution, and to determine if this treatment when used in the broader community could reproduce the results achieved in the Treatment of Age-related Macular Degeneration (AMD) with PDT (TAP) study., Methods: A record of all patients who first received PDT with verteporfin at The Royal Victorian Eye and Ear Hospital between the time of its introduction in February 2000 and February 2001 was prospectively maintained. The medical charts of these cases were reviewed and fluorescein angiograms were graded. Eyes with AMD were classified into three groups: TAP comparable if they had predominantly classic subfoveal choroidal neovascularization (CNV) and visual acuity between 6/12 and 6/60; VIP comparable if they had occult but no classic subfoveal CNV and visual acuity better than 6/36; and PDT ineligible if they fell outside recommended eligibility guidelines of the TAP/VIP studies. The main outcome measure was visual acuity change, with total number of treatments a secondary outcome variable., Results: A total of 136 eyes of 130 patients began PDT during this period. The baseline angiogram and clinical data were available for 123 eyes (90%), and these were reviewed. Fourteen eyes had non-AMD related CNV, while 109 eyes of 105 patients had AMD. Of the 109 AMD related lesions, 72 (66%) were TAP comparable, six (5.5%) were VIP comparable and 31 (28%) were PDT ineligible. At the 12-month visit the proportion of TAP comparable eyes with same or better vision was 36/72 (50%), compared to 13/31 (42%) of the PDT ineligible eyes (P = 0.45). Only 30/72 (42%) of the TAP comparable eyes were still undergoing regular angiographic and clinical assessment (similar to the TAP protocol) at the time of the 12 month visit. The number of these who had same or better vision at 12 months was 17/30 (57%) compared to 19/42 (44%) TAP comparable eyes without regular angiographic follow up to 12 months (P = 0.37). CONCLUSDIONS; When used according to the guidelines established by the TAP study, the visual acuity results with PDT approached those achieved in the TAP study. When eyes were either enrolled outside the TAP study eligibility guidelines, or were not actively followed up over the 12-month period as per TAP study guidelines, the visual outcome was similar to natural history of CNV secondary to AMD.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in individuals 50 years and older in the developed world. Choroidal neovascularization (CNV) in exudative AMD is responsible for the majority of severe vision loss. Until recently, laser photocoagulation was the only well-established and widely accepted treatment for CNV. However, it is beneficial only for a small subset of patients, has a high rate of CNV persistence and recurrence and results in iatrogenic, collateral damage to the overlying retina. These issues make it difficult to recommend in the case of subfoveal lesions. Consequently, numerous experimental therapeutic interventions are under investigation with the common objective of destroying the CNV but leaving the foveal neurosensory retina intact. Treatment modalities can be grouped into five major categories: photodynamic therapy; radiotherapy; transpupillary thermotherapy; anti-angiogenic and angiostatic agents; and surgical intervention. The present review aims to explain the rationale behind these new treatments, analyse the evidence for their safety and efficacy, determine their stage of development and indicate in which patients they are potentially useful.

Background: A single base change within the EFEMP1 gene has been associated with malattia leventinese and Doyne honeycomb retinal dystrophy, two dominantly inherited macular diseases with early onset drusen. The aim of this study was to determine whether the same disease allele was also associated with other forms of early onset drusen or familial cases of age-related macular degeneration., Methods: Thirteen index cases of early onset drusen together with 15 other family members were examined. In addition, 54 familial cases of age-related macular degeneration were examined. Blood was taken for DNA analysis and screened for the Arg345Trp disease-associated allele of the EFEMP1 gene. Twenty-four cases of malattia leventinese or Doyne honeycomb retinal dystrophy were also screened as positive controls. Another 150 ethnicity- and age-matched individuals acted as controls., Results: The Arg345Trp disease-associated allele in the EFEMP1 gene was confirmed in individuals with malattia leventinese and Doyne honeycomb retinal dystrophy. However, involvement of this allele was not evident in either early onset drusen or familial age-related macular degeneration., Conclusions: The Arg345Trp disease-associated allele of the EFEMP1 gene does not appear to be associated with cases of early onset drusen that fall outside the diagnosis of malattia leventinese or Doyne honeycomb retinal dystrophy, nor does it appear to play a role in familial age-related macular degeneration. These findings do not exclude the involvement of other alleles of the EFEMP1 gene in either phenotype. The genetic mechanisms involved in the heterogeneous group of early onset drusen remain to be elucidated but should lead to insights into the genetic causes of macular diseases.