Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration.

There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies are needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with geographic atrophy and healthy individuals were differentiated to retinal pigment epithelium. Integrating transcriptional profiles of 127,659 retinal pigment epithelium cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identify 445 expression quantitative trait loci in cis that are asssociated with disease status and specific to retinal pigment epithelium subpopulations. Transcriptomics and proteomics approaches identify molecular pathways significantly upregulated in geographic atrophy, including in mitochondrial functions, metabolic pathways and extracellular cellular matrix reorganization. Five significant protein quantitative trait loci that regulate protein expression in the retinal pigment epithelium and in geographic atrophy are identified - two of which share variants with cis- expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration. Investigation of mitochondrial metabolism confirms mitochondrial dysfunction as a core constitutive difference of the retinal pigment epithelium from patients with geographic atrophy. This study uncovers important differences in retinal pigment epithelium homeostasis associated with geographic atrophy.

The VEGF Treatment of AMD Switch Study (The vTAS Study).

PURPOSE: To evaluate the effect of aflibercept on anatomic and visual outcomes in patients with choroidal neovascularization (CNV) previously treated with intravitreal ranibizumab with persistent fluid on optical coherence tomography (OCT). DESIGN: Prospective, open-label study. METHODS: Eighteen patients (19 eyes) with CNV being treated with monthly ranibizumab, with persistent fluid on OCT, were switched to intravitreal aflibercept injections at intervals of up to 8 weeks. The primary outcome was the proportion of patients maintaining vision [<5 letter loss in visual acuity (VA)] at week 48. Secondary outcomes included the change in VA and central macular thickness (CMT) and the frequency of treatment necessary along with the safety of intravitreal aflibercept. RESULTS: Forty-eight weeks after switching to aflibercept, 16/19 eyes had maintained VA. There was a median increase in vision of 5 letters [interquartile range (IQR): 0, 15; P = 0.06)] and median CMT was reduced from 313 µm (IQR: 214, 334) to 258 µm (IQR: 200, 299; P = 0.02). After stratification by fluid location the reduction in CMT was statistically significant for eyes with intraretinal fluid (IRF) at baseline [median change, -25 µm (IQR: -14, -64); P = 0.01]. Macular volume within 6 mm of the fovea (CMTVol) was significantly reduced in eyes with subretinal fluid (SRF) [-0.20 mm³ (IQR: -1.45, -0.05); P = 0.03]. CONCLUSIONS: In this small cohort of eyes, switching to aflibercept seemed beneficial. The majority maintained or improved vision and eyes with IRF or SRF had significant reductions in macular edema. However, visual improvement was not always indicative of anatomical improvement.

Treatment of age-related macular degeneration.

Age-related macular degeneration (AMD) is the greatest cause of legal blindness in the western world. Established treatments include argon laser photocoagulation of extrafoveal choroidal neovascularisation (CNV) and photodynamic therapy of selected sub-foveal CNV. Newer approaches are targeting the angiogenic pathway in CNV development. Currently, other treatment modalities, such as radiotherapy and transpupillary thermotherapy do not have a clear role to play. Surgical options are experimental and only available in some centres for selected patients. Prevention of AMD remains elusive. Dietary supplements may have a role, while statins and prophylactic laser photocoagulation of drusen remain experimental. This paper explains the principles behind these approaches.

Australian Angiogram Review Panel--monitoring the use of photodynamic therapy with verteporfin.

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.

Utilization of eye care services by Victorians likely to benefit from eye care.

AIM: To assess the utilization of eye care services by Australians most likely to benefit from eye assessment. METHODS: The Melbourne Visual Impairment Project was a population-based study that collected demographic, health and vision-related information including use of eye care services. A standardized detailed ophthalmic examination was performed. Utilization of eye care services by those who might most benefit from eye care was assessed and compared to the general population. These participants include those with undiagnosed glaucoma, unoperated visually significant cataract, undercorrected refractive error, diabetes mellitus, age-related macular degeneration and visual acuity < 6/12. Sociodemographic characteristics were assessed for their influence on eye care utilization among these participants. RESULTS: A total of 4744 urban and rural residents participated (86% of those eligible) and 4612 (83% of total eligible) of these had a complete data set for the use of eye care services and were included. There were 933 participants (20.2%) who did not report eye assessment in the previous 5 years, and 891 participants (19.3%) had one or more aforementioned conditions potentially benefiting from eye care. Of these, between 34.4% and 59.4% reported no examination in the previous year and between 9% and 25% reported no examination within the previous 5 years. These participants were more likely to seek eye care within the short term (1 year) if they had a family history of eye disease, otherwise a noticed change in vision was the main influence in the longer term (2-5 years). Male participants, younger participants and those whose main spoken language was not English were less likely to seek eye care in the longer term. CONCLUSIONS: In Victoria 19% of those >40 years of age have potentially unmanaged eye disease including glaucoma, unoperated visually significant cataract, undercorrected refractive error, age-related macular degeneration, diabetes mellitus or visual acuity < 6/12. A substantial proportion of these report no eye assessment in the previous 1, 2 or 5 years or ever before. Younger age, male sex and main language other than English make assessment less likely. Many may have these conditions despite having had a recent eye assessment.