Real-life patient journey in neovascular age-related macular degeneration: a narrative medicine analysis in the Italian setting.

OBJECTIVES: To investigate the real-life experience of patients affected by neovascular age-related macular degeneration (nAMD), in the healthcare pathway for the management of the disease, using a "patient journey" and narrative method approach. METHODS: The patient journey of subjects affected by nAMD was designed using a process-mapping methodology involving a team from 11 Italian centres. Subsequently, narratives were collected from nAMD patients and family members. The interviews were analyzed using the narrative medicine methodology. RESULTS: Eleven specialized retina centres across Italy were involved and 205 narratives collected. In 29% of cases, patients underestimated their symptoms or attributed them to non-pathological causes, thus delaying the specialist consultation. The delay in accessing to care was due to a lack of awareness of this disease (50% of the participants didn't know what nAMD is) and to critical issues faced at first visit (long waiting lists, failed diagnosis, underestimation of the problem). Despite anti-VEGF therapies were perceived as effective in improving or stabilizing vision in 91% of narratives collected, 77% of patients still reduced or ceased daily activities such as reading and driving. Within the pathway of care there was not a multidisciplinary approach, and the patients were treated just by the ophthalmologist. CONCLUSIONS: nAMD may significantly affect the quality of life of affected patients, both from a functional and psychological point of view. The narrative medicine approach highlights some critical points in the healthcare journey of nAMD patients and represents a useful background in implementing patient management algorithms and pathways of care.

Prevalence and risk factors for myopia and other refractive errors in an adult population in southern India.

PURPOSE: To investigate prevalence and risk factors for myopia, hyperopia and astigmatism in southern India. METHODS: Randomly sampled villages were enumerated to identify people aged ≥40 years. Participants were interviewed for socioeconomic and lifestyle factors and attended a hospital-based ophthalmic examination including visual acuity measurement and objective and subjective measurement of refractive status. Myopia was defined as spherical equivalent (SE) worse than -0.75 dioptres (D), hyperopia as SE ≥+1D and astigmatism as cylinder <-0.5. RESULTS: The age-standardised prevalences of myopia, hyperopia and astigmatism were 35.6% (95% CI: 34.7-36.6), 17.0% (95% CI: 16.3-17.8) and 32.6 (29.3-36.1), respectively. Of those with myopia (n = 1490), 70% had advanced cataract. Of these, 79% had presenting visual acuity (VA) less than 6/18 and after best correction, 44% of these improved to 6/12 or better and 27% remained with VA less than 6/18. In multivariable analyses (excluding patients with advanced cataract), increasing nuclear opacity score, current tobacco use, and increasing height were associated with higher odds of myopia. Higher levels of education were associated with increased odds of myopia in younger people and decreased odds in older people. Increasing time outdoors was associated with myopia only in older people. Increasing age and female gender were associated with hyperopia, and nuclear opacity score, increasing time outdoors, rural residence and current tobacco use with lower odds of hyperopia. After controlling for myopia, factors associated with higher odds of astigmatism were age, rural residence, and increasing nuclear opacity score and increasing education with lower odds. CONCLUSIONS: In contrast to high-income settings and in agreement with studies from low-income settings, we found a rise in myopia with increasing age reflecting the high prevalence of advanced cataract.

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing.

To assess the clinical utility of targeted Next-Generation Sequencing (NGS) for the diagnosis of Inherited Retinal Dystrophies (IRDs), a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Stargardt Disease (STGD), Best Macular Dystrophy (BMD), Usher Syndrome (USH), and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS). Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

Stem cells as source for retinal pigment epithelium transplantation.

Inherited maculopathies, age related macular degeneration and some forms of retinitis pigmentosa are associated with impaired function or loss of the retinal pigment epithelium (RPE). Among potential treatments, transplantation approaches are particularly promising. The arrangement of RPE cells in a well-defined tissue layer makes the RPE amenable to cell or tissue sheet transplantation. Different cell sources have been suggested for RPE transplantation but the development of a clinical protocol faces several obstacles. The source should provide a sufficient number of cells to at least recover the macula area. Secondly, cells should be plastic enough to be able to integrate in the host tissue. Tissue sheets should be considered as well, but the substrate on which RPE cells are cultured needs to be carefully evaluated. Immunogenicity can also be an obstacle for effective transplantation as well as tumorigenicity of not fully differentiated cells. Finally, ethical concerns may represent drawbacks when embryo-derived cells are proposed for RPE transplantation. Here we discuss different cell sources that became available in recent years and their different properties. We also present data on a new source of human RPE. We provide a protocol for RPE differentiation of retinal stem cells derived from adult ciliary bodies of post-mortem donors. We show molecular characterization of the in vitro differentiated RPE tissue and demonstrate its functionality based on a phagocytosis assay. This new source may provide tissue for allogenic transplantation based on best matches through histocompatibility testing.

EPHA2 polymorphisms and age-related cataract in India.

OBJECTIVE: We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India. METHODS: We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location. RESULTS: 7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract. CONCLUSIONS: Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.

Prevalence and risk factors for vitamin C deficiency in north and south India: a two centre population based study in people aged 60 years and over.

BACKGROUND: Studies from the UK and North America have reported vitamin C deficiency in around 1 in 5 men and 1 in 9 women in low income groups. There are few data on vitamin C deficiency in resource poor countries. OBJECTIVES: To investigate the prevalence of vitamin C deficiency in India. DESIGN: We carried out a population-based cross-sectional survey in two areas of north and south India. Randomly sampled clusters were enumerated to identify people aged 60 and over. Participants (75% response rate) were interviewed for tobacco, alcohol, cooking fuel use, 24 hour diet recall and underwent anthropometry and blood collection. Vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid. We categorised vitamin C status as deficient (<11 µmol/L), sub-optimal (11-28 µmol/L) and adequate (>28 µmol/L). We investigated factors associated with vitamin C deficiency using multivariable Poisson regression. RESULTS: The age, sex and season standardized prevalence of vitamin C deficiency was 73.9% (95% confidence Interval, CI 70.4,77.5) in 2668 people in north India and 45.7% (95% CI 42.5,48.9) in 2970 from south India. Only 10.8% in the north and 25.9% in the south met the criteria for adequate levels. Vitamin C deficiency varied by season, and was more prevalent in men, with increasing age, users of tobacco and biomass fuels, in those with anthropometric indicators of poor nutrition and with lower intakes of dietary vitamin C. CONCLUSIONS: In poor communities, such as in our study, consideration needs to be given to measures to improve the consumption of vitamin C rich foods and to discourage the use of tobacco.

Inverse association of vitamin C with cataract in older people in India.

OBJECTIVE: To examine the association between vitamin C and cataract in the Indian setting. DESIGN: Population-based cross-sectional analytic study. PARTICIPANTS: A total of 5638 people aged ≥60 years. METHODS: Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography. MAIN OUTCOME MEASURES: Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract. RESULTS: Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51-0.74; P=1.1×10(-6)). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, ß-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57-0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54-0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54-0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45-0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract. CONCLUSIONS: We found a strong association with vitamin C and cataract in a vitamin C-depleted population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prevalence of cataract in an older population in India: the India study of age-related eye disease.

PURPOSE: To describe the prevalence of cataract in older people in 2 areas of north and south India. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Randomly sampled villages were enumerated to identify people aged ≥ 60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination. METHODS: The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III). MAIN OUTCOME MEASURES: Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥ 4 for nuclear cataract, ≥ 3 for cortical cataract, and ≥ 2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract. RESULTS: The prevalence of unoperated cataract in people aged ≥ 60 was 58% in north India (95% CI, 56-60) and 53% (95% CI, 51-55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46-50) in north India and 38% (95% CI, 37-40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20-23) and 17% (95% CI, 16-19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7-9) and 10.2% (95% CI, 9-11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002). CONCLUSIONS: We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery.

Prevalence of early and late age-related macular degeneration in India: the INDEYE study.

PURPOSE: To estimate the prevalence of early and late age-related macular degeneration (AMD) in India. METHODS: Of 7518 people aged 60 years and older identified from randomly sampled villages in North and South India, 5853 (78%) attended an eye examination including fundus photography. Fundus images were graded according to the Wisconsin Age-Related Maculopathy Grading System. RESULTS: Fundus images were ungradable in 1587 people, mainly because of cataract. People 80 years of age and older were less likely to attend the eye examination and more likely to have ungradable images. For ages 60 to 79 years, the percent prevalence (95% confidence interval [CI]) were late AMD 1.2 (0.8-1.5); and early AMD: grade 1 (soft distinct drusen or pigmentary irregularities), 39.3 (37.2-41.5); grade 2 (soft distinct drusen with pigmentary irregularities or soft indistinct or reticular drusen), 6.7 (5.8-7.6); and grade 3 (soft indistinct or reticular drusen with pigmentary irregularities), 0.2 (0.1-0.4). For ages 80 and older, the respective percent prevalence was: late AMD, 2.5 (0.4-4.7); and early AMD: grade 1, 43.1(35.7-50.6); grade 2, 8.1 (4.3-12.0); and grade 3, 0.5 (0-1.5). CONCLUSIONS: The prevalence of early AMD (grades 1 and 2) is similar to that observed in Western populations, but grade 3 appears to be lower. The prevalence of late AMD is comparable to that in Western populations in the age group 60 to 79 years. It is likely that the prevalence in the 80 and older age group is underestimated.

Blood levels of vitamin C, carotenoids and retinol are inversely associated with cataract in a North Indian population.

PURPOSE: To examine the association of blood antioxidants with cataract. METHODS: Cross-sectional study of people aged >or=50 years identified from a household enumeration of 11 randomly sampled villages in North India. Participants were interviewed for putative risk factors (tobacco, alcohol, biomass fuel use, sunlight exposure, and socioeconomic status) and underwent lens photography and blood sampling. Lens photographs (nuclear, cortical, and posterior subcapsular) were graded according to the Lens Opacities Classification System (LOCS II). Cataract was defined as LOCS II grade >or=2 for any opacity or ungradable, because of dense opacification or history of cataract surgery. People without cataract were defined as LOCS II <2 on all three types of opacity, with absence of previous surgery. RESULTS: Of 1443 people aged >or=50 years, 94% were interviewed, 87% attended an eye examination, and 78% gave a blood sample; 1112 (77%) were included in the analyses. Compared with levels in Western populations, antioxidants were low, especially vitamin C. Vitamin C was inversely associated with cataract. Odds ratios (OR) for the highest (>or=15 micromol/L) compared with the lowest (

Prevalence of lens opacities in North India: the INDEYE feasibility study.

PURPOSE: To obtain estimates of the prevalence of lens opacities in an Indian setting by using photographically acquired lens images. METHODS: In 11 randomly sampled villages from a rural district of Haryana, North India, 1443 people (median age 60 years), 52% women, were identified from enumeration of the > or =50-year age group; 87% attended an eye examination. Digital images of cortical and posterior subcapsular opacities and photographs of nuclear opacities were graded using the Lens Opacity Classification System (LOCS) II. The prevalence of opacities was based on a grade of 2 or higher in the worse eye for nuclear, cortical, or posterior subcapsular opacities. RESULTS: Of the participants, 1071 people had gradable images; a further 163 had undergone surgery or had dense opacities. Nuclear opacities were the most common type, with an overall prevalence of 56.9% (95% CI, 53.0-60.6). Posterior subcapsular opacities occurred in 20.6% (95% CI, 17.9-25.8) and cortical opacities in 21.6% (95% CI, 17.9-25.8). Prevalence rose steeply with age for all opacities and was higher in the women than in the men for cortical opacities (P = 0.03). The prevalence of any type of lens opacity including surgical cases and dense opacities was 75.3% (95% CI, 71.4-78.81). CONCLUSIONS: These results highlight the substantial excess of lens opacities in India compared with Western populations.