Quality of life impact of eye diseases: a Save Sight Registries study.

BACKGROUND: The objectives of this study were to evaluate the quality-of-life (QoL) impact of eye diseases (keratoconus; neovascular age-related macular degeneration, AMD; retinal vein occlusion, RVO; and diabetic macular edema, DME) using the Impact of Vision Impairment (IVI) questionnaire, and to determine the relationship between the IVI scores and visual acuity. METHODS: This cross-sectional, multicentre, real-world study utilised the prospective, web-based Save Sight Registries. The IVI was completed by 1557 patients: 307 with keratoconus, 1049 with AMD, 148 with RVO and 53 with DME. Statistical analysis included Rasch analysis, Welch t-test, one-way ANOVA, Tukey's test, Pearson correlation, and multiple regression. RESULTS: The IVI scales (Overall; Visual Function, VF; Emotional, EM) had robust psychometric properties. The keratoconus patients had the worst Overall (adjusted mean: 48.2 vs. DME 58.8, RVO 64.6, AMD 67.6 units), VF (47.7 vs. DME 59.4, RVO 65.9, AMD 68.9 units) and EM (50.8 vs. DME 63.1, RVO 69.2, AMD 71.8 units) scores (all p < 0.05). The IVI scales scores weakly correlated with better and worse eye visual acuity (Pearson's r 0.24-0.39, all p < 0.05). The correlations were similar in the better eye (Overall 0.35, VF 0.39, EM 0.24) and the worse eye (Overall 0.31, VF 0.33, EM 0.25) visual acuity. Correlations with visual acuity were stronger for VF than for the EM scores. CONCLUSIONS: The IVI was a psychometrically robust QoL questionnaire. Keratoconus patients had worse IVI scores than patients with retinal diseases. The low strength of correlations between visual acuity and QoL scores, although statistically significant, suggested that a complex relationship exists.

The Decreasing Prevalence of Nonrefractive Visual Impairment in Older Europeans: A Meta-analysis of Published and Unpublished Data.

TOPIC: To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 55 years of age and older. CLINICAL RELEVANCE: Few visual impairment and blindness prevalence estimates are available for the European population. In addition, many of the data collected in European population-based studies currently are unpublished and have not been included in previous estimates. METHODS: Fourteen European population-based studies participating in the European Eye Epidemiology Consortium (n = 70 723) were included. Each study provided nonrefractive visual impairment and blindness prevalence estimates stratified by age (10-year strata) and gender. Nonrefractive visual impairment and blindness were defined as best-corrected visual acuity worse than 20/60 and 20/400 in the better eye, respectively. Using random effects meta-analysis, prevalence rates were estimated according to age, gender, geographical area, and period (1991-2006 and 2007-2012). Because no data were available for Central and Eastern Europe, population projections for numbers of affected people were estimated using Eurostat population estimates for European high-income countries in 2000 and 2010. RESULTS: The age-standardized prevalence of nonrefractive visual impairment in people 55 years of age or older decreased from 2.22% (95% confidence interval [CI], 1.34-3.10) from 1991 through 2006 to 0.92% (95% CI, 0.42-1.42) from 2007 through 2012. It strongly increased with age in both periods (up to 15.69% and 4.39% in participants 85 years of age or older from 1991 through 2006 and from 2007 through 2012, respectively). Age-standardized prevalence of visual impairment tended to be higher in women than men from 1991 through 2006 (2.67% vs. 1.88%), but not from 2007 through 2012 (0.87% vs. 0.88%). No differences were observed between northern, western, and southern regions of Europe. The projected numbers of affected older inhabitants in European high-income countries decreased from 2.5 million affected individuals in 2000 to 1.2 million in 2010. Of those, 584 000 were blind in 2000, in comparison with 170 000 who were blind in 2010. CONCLUSIONS: Despite the increase in the European older population, our study indicated that the number of visually impaired people has decreased in European high-income countries in the last 20 years. This may be the result of major improvements in eye care and prevention, the decreasing prevalence of eye diseases, or both.

Morphologic Criteria of Lesion Activity in Neovascular Age-Related Macular Degeneration: A Consensus Article.

Intravitreal antivascular endothelial growth factor drugs represent the current standard of care for neovascular age-related macular degeneration (nAMD). Individualized treatment regimens aim at obtaining the same visual benefits of monthly injections with a reduced number of injections and follow-up visits, and, consequently, of treatment burden. The target of these strategies is to timely recognize lesion recurrence, even before visual deterioration. Early detection of lesion activity is critical to ensure that clinical outcomes are not compromised by inappropriate delays in treatment, but questions remain on how to effectively monitor the choroidal neovascularization (CNV) activity. To assess the persistence/recurrence of lesion activity in patients undergoing treatment for nAMD, an expert panel developed a decision algorithm based on the morphological features of CNV. After evaluating all current retinal imaging techniques, the panel identified optical coherent tomography as the most reliable tool to ascertain lesion activity when funduscopy is not obvious.

Non-syndromic isolated dominant optic atrophy caused by the p.R468C mutation in the AFG3 like matrix AAA peptidase subunit 2 gene.

Autosomal dominant optic atrophy (DOA) is the most frequent form of hereditary optic atrophy, a disease presenting with considerable inter- and intra-familial clinical variability. Although a number of mutations in different genes are now known to cause DOA, many cases remain undiagnosed. In an attempt to identify the underlying genetic defect, whole exome sequencing was performed in a 19-year-old male that had been affected by isolated DOA since childhood. The exome sequencing revealed a pathogenic mutation (p.R468C, c.1402C>T) in the AFG3 like matrix AAA peptidase subunit 2 (AFG3L2) gene, a gene known to be associated with spinocerebellar ataxia. The patient did not show any signs other than DOA. Thus, the result demonstrates the possibility that mutations in the AFG3L2 gene may be a cause of isolated autosomal DOA.

Long-term rearrangement of retinal structures in a novel mutation of X-linked retinoschisis.

The aim of the present study was to report a novel mutation in the retinoschisin 1 (RS1) gene in a Caucasian family affected by X-linked juvenile retinoschisis (XLRS) and to describe the long-term modification of retinal structure. Two brothers with an early onset maculopathy were diagnosed with XLRS. Fundus photography, fluorescein angiography, spectral domain optical coherence tomography and electroretinogram analyses were performed. Their sister was also examined. All subjects were screened for mutations in the RS1 gene. XLRS patients demonstrated a marked reduction of best-corrected visual acuity. SD-OCT scans reported a cystic degeneration primarily involving the inner nuclear layer, though some cysts were detected in the outer plexiform layer and in the ganglion cell layer. During the ten-year follow-up, a progressive retinal thickening and coalescence of the cysts was observed. Genetic testing revealed a novel mutation (p.Ile212Asn) in the RS1 gene in both XLRS patients, whereas their sister was not a genetic carrier. Several mutations of the RS1 gene were recognized to be responsible for XLRS. Although the correspondence between genotype and phenotype is still under debate, is reasonable that siblings affected by XLRS could share other genetic and/or epigenetic factors capable to influence clinical course of the disease.

Occult macular dystrophy in an Italian family carrying a mutation in the RP1L1 gene.

Occult macular dystrophy (OMD) is an inherited macular disease characterized by progressive visual decline with the absence of visible retinal abnormalities. Typical alterations of the retinal structure are detectable by spectral domain optical coherence tomography (SD­OCT). Mutations in the RP1L1 gene have been identified to be responsible for the disease in Asian subjects. The present study assessed the role of mutations in the RP1L1 gene in an Italian family with OMD. One patient with OMD and five related subjects (two male offspring affected by progressive visual decline and three asymptomatic siblings of the patient) were subjected to complete ophthalmological examination. SD­OCT was also performed. All subjects were screened for OMD­associated genetic mutations in the RP1L1 gene. The OMD patient and the two symptomatic offspring presented with a reduced best­corrected visual acuity. Although no fundus abnormalities were observed, SD­OCT examination showed that the external limiting membrane and the inner segment/outer segment band were not clearly identifiable and a focal disruption of the photoreceptor layer was present. The degree of photoreceptor alterations was correlated with the severity of visual impairment. Clinical and tomographic results in the three asymptomatic relatives were normal. A p.Arg45Trp mutation in the RP1L1 gene was identified in the OMD patient, in the two symptomatic offspring and also in two of the asymptomatic siblings of the patient. The identification of RP1L1 mutations in subjects with OMD may improve the accuracy of diagnosis of this rare condition and may aid in enhancing the efficacy of genetic counseling.

Combined effects of genetic and non-genetic risk factors affect response to ranibizumab in exudative age-related macular degeneration.

PURPOSE: To investigate whether genetic and non-genetic risk factors influence 12-month response to ranibizumab treatment for exudative age-related macular degeneration (AMD). METHODS: A cohort of 94 Caucasian patients with unilateral exudative AMD received intravitreal ranibizumab. After a three-injection loading phase, a PRN regimen was followed. Patients were genotyped for three single-nucleotide polymorphisms: CFH rs1061170, ARMS2 rs10490924 and C3 rs2230199. Non-genetic risk factors [choroidal neovascularization (CNV) phenotype, smoking habit, hypertension and body mass index] were considered. The selected end-point was the 12-month variation of number of ETDRS letters. RESULTS: Complement factor H (CFH) risk alleles, smoking history and arterial hypertension each independently influenced treatment response, with worse 12-month BCVA outcomes (p = 0.036, 0.037, 0.043, respectively). A significant cumulative effect of these risk factors was also observed: patients homozygous for the CFH risk alleles and with a positive smoking history showed a mean loss of 8.0 ETDRS letters (p = 0.010). Patients with CFH risk alleles, smoking history and hypertension had a mean loss of 13.9 ETDRS letters (p = 0.013). CNV phenotypes did not influence visual outcomes, nor were they associated with other genetic/non-genetic risk factors. CONCLUSIONS: Complement factor H risk alleles, smoking history and hypertension affect the mid-term response to ranibizumab in exudative AMD.

Mitomycin C-assisted photorefractive keratectomy in high myopia: a long-term safety study.

PURPOSE: To evaluate the long-term corneal safety of topical mitomycin C (MMC) used during photorefractive keratectomy to prevent haze formation in highly myopic eyes. METHODS: Twenty-eight patients with bilateral high myopia underwent photorefractive keratectomy. One eye was randomly assigned to intraoperative 0.02% MMC and the fellow eye to conventional treatment. Each eye was checked at baseline and at 5 years after surgery using in vivo corneal confocal microscopy. RESULTS: At baseline, the endothelial cell density was 2970 ± 295 cells per square millimeter in the MMC-treated eyes and 2839 ± 323 cells per square millimeter in the control eyes. At 5 years, it was 2803 ± 307 and 2780 ± 264 cells per square millimeter, respectively (P = 0.27). The number of corneal nerve fibers was 3.9 ± 1.6 in the MMC-treated eyes and 4.4 ± 1.3 in the control eyes. At 5 years, it was 3.0 ± 1.6 and 2.7 ± 1.3, respectively (P = 0.15). The density of corneal nerves was 9600 ± 2915 µm/mm(2) in the MMC-treated eyes and 11,352 ± 3898 µm/mm(2) in the control eyes. At 5 years, the density was higher in the MMC-treated eyes (6790 ± 2447 µm/mm(2)) than in the control eyes (6024 ± 2977 µm/mm(2)) (P = 0.003). The number of nerve beadings at baseline was 12.9 ± 1.7/100 µm in the MMC-treated eyes and 12.3 ± 2.0/100 µm in the control eyes. At 5 years, it was 9.9 ± 2.6/100 and 9.4 ± 2.9/100 µm, respectively (P = 1.00). At 5 years, corneal nerve branching and tortuosity were similar in the 2 groups (P = 0.88 and 0.54, respectively). Epithelium thickness remained statistically unchanged (P = 0.69). CONCLUSIONS: Intraoperative use of topical 0.02% MMC compared with standard treatment does not induce significant long-term corneal changes, as assessed by in vivo corneal confocal microscopy.

Confocal microscopy of corneal sub-basal nerve plexus: a quantitative and qualitative analysis in healthy and pathologic eyes.

PURPOSE: To validate corneal sub-basal nerve plexus examination by in vivo corneal confocal microscopy. METHODS: Five parameters of corneal sub-basal nerve plexus in 250 human eyes (nerve fiber length, number of fibers, number of beadings, branching pattern, fiber tortuosity) acquired using in vivo corneal confocal microscopy (Confoscan 4.0; NIDEK Co Ltd) were analyzed. The first operator repeated the parameter analysis twice, performing the 2 evaluations 4 weeks apart. The second operator analyzed the cases once. RESULTS: Intraoperator reproducibility of nerve fiber length, number of fibers, and number of beadings (intraclass correlation coefficient [ICC] = 0.96, 0.96, and 0.93, respectively) and interoperator reproducibility (ICC = 0.94, 0.95, and 0.87, respectively) were very good. Intraoperator reproducibility for branching pattern was good (ICC = 0.74), whereas interoperator reproducibility was very good (ICC = 0.81). Reproducibility of fiber tortuosity was good both at intra- and interoperator levels (ICC = 0.69 and 0.60, respectively). CONCLUSIONS: Corneal confocal microscopy with the NIDEK Confoscan 4.0 represents an in vivo, noninvasive, and reproducible diagnostic technique for the analysis of sub-basal corneal nerve plexus. Methods used to analyze quantitative and qualitative variables were highly reproducible.

Long-term effects on corneal keratocytes of mitomycin C during photorefractive keratectomy: a randomized contralateral eye confocal microscopy study.

PURPOSE: To evaluate the long-term side effects of mitomycin C (MMC) assisted photorefractive keratectomy (PRK) on corneal keratocytes of highly myopic eyes. METHODS: Twenty-eight patients with bilateral myopia from -7.00 to -14.25 diopters (D) underwent PRK on both eyes, one eye of each patient received topical application of 0.02% MMC for 2 minutes immediately after the PRK procedure. Corneal keratocyte density was quantified by corneal confocal microscopy at baseline and 5 years postoperatively. RESULTS: Photorefractive keratectomy reduced keratocyte density in the most anterior stromal layer, without a statistically significant difference between MMC and standard treated eyes. Posterior stromal layers showed no signs of keratocyte loss with either techniques. CONCLUSIONS: Phototherapeutic keratectomy with 0.02% topical MMC has no significant side effects on corneal keratocytes compared to standard PRK, as documented by in vivo corneal confocal microscopy.