Genetic and environmental factors related to the development of myopic maculopathy in Spanish patients.

High myopia and the subsequent degenerative changes of the retina, choroid, and sclera, known as myopic maculopathy (MM), are a serious visual problem in many Asian countries, and are beginning to be so in the south of Europe, especially in the Mediterranean. It is therefore necessary to carry out genetic and environmental studies to determine the possible causes of this disease. This study aims to verify if the genetic factors that have been most related to Asian populations are also associated in two Spanish cohorts. Eight SNPs from six genes (PAX6, SCO2, CCDC102B, BLID, chromosome 15q14, and COL8A1) along with demographic, ophthalmic and environmental factors were analysed in two cohorts from a total of 365 highly myopic subjects and 177 control subjects. The genetic analysis showed that COL8A1 SNP rs13095226 was associated with the development of choroidal neovascularization (CNV) and also seems to play an important role in the increase of axial length. The SNP rs634990 of chromosome 15q14 also showed a significant association with MM, although this was lost after the Bonferroni correction. Additional demographic and environmental factors, namely age, sex, smoking status, and pregnancy history, were also found to be associated with MM and CNV in this population.

Evaluation of 10 AMD Associated Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes.

Choroidal neovascularization (CNV) commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs) located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE), and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population. Univariate and multivariate logistic regression analysis adjusted for age, sex and hypertension was performed for each allele, genotype and haplotype frequency analysis. We found that in the univariate analysis that both single-nucleotide polymorphisms in COL8A1 gene (rs13095226 and rs669676) together with age, sex and hypertension were significantly associated with myopic CNV development in Spanish patients (p<0.05). After correcting for multiple testing none of the polymorphisms studied remained significantly associated with myopic CNV (p>0.05); however, analysis of the axial length between genotypes of rs13095226 revealed an important influence of COL8A1 in the development of CNV in high myopia. Furthermore we conducted a meta-analysis of COL8A1, CFI and LIPC genes SNPs (rs669676, rs10033900 and rs10468017) and found that only rs669676 of these SNPs were associated with high myopia neovascularization.

A Diagnostic Calculator for Detecting Glaucoma on the Basis of Retinal Nerve Fiber Layer, Optic Disc, and Retinal Ganglion Cell Analysis by Optical Coherence Tomography.

PURPOSE: The purpose of this study was to develop and validate a multivariate predictive model to detect glaucoma by using a combination of retinal nerve fiber layer (RNFL), retinal ganglion cell-inner plexiform (GCIPL), and optic disc parameters measured using spectral-domain optical coherence tomography (OCT). METHODS: Five hundred eyes from 500 participants and 187 eyes of another 187 participants were included in the study and validation groups, respectively. Patients with glaucoma were classified in five groups based on visual field damage. Sensitivity and specificity of all glaucoma OCT parameters were analyzed. Receiver operating characteristic curves (ROC) and areas under the ROC (AUC) were compared. Three predictive multivariate models (quantitative, qualitative, and combined) that used a combination of the best OCT parameters were constructed. A diagnostic calculator was created using the combined multivariate model. RESULTS: The best AUC parameters were: inferior RNFL, average RNFL, vertical cup/disc ratio, minimal GCIPL, and inferior-temporal GCIPL. Comparisons among the parameters did not show that the GCIPL parameters were better than those of the RNFL in early and advanced glaucoma. The highest AUC was in the combined predictive model (0.937; 95% confidence interval, 0.911-0.957) and was significantly (P = 0.0001) higher than the other isolated parameters considered in early and advanced glaucoma. The validation group displayed similar results to those of the study group. CONCLUSIONS: Best GCIPL, RNFL, and optic disc parameters showed a similar ability to detect glaucoma. The combined predictive formula improved the glaucoma detection compared to the best isolated parameters evaluated. The diagnostic calculator obtained good classification from participants in both the study and validation groups.

Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management.

Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder associated with thyroid disease which affects ocular and orbital tissues. GO follows a biphasic course in which an initial active phase of progression is followed by a subsequent partial regression and a static inactive phase. Although the majority of GO patients have a mild, self-limiting, and nonprogressive ocular involvement, about 3-7% of GO patients exhibit a severe sight-threatening form of the disease due to corneal exposure or compressive optic neuropathy. An appropriate assessment of both severity and activity of the disease warrants an adequate treatment. The VISA (vision, inflammation, strabismus, and appearance), and the European Group of Graves' Orbitopathy (EUGOGO) classifications are the two widely used grading systems conceived to assess the activity and severity of GO and guide the therapeutic decision making. A critical analysis of classification, assessment, and management systems is reported. A simplified "GO activity assessment checklist" for routine clinical practice is proposed. Current treatments are reviewed and management guidelines according to the severity and activity of the disease are provided. New treatment modalities such as specific monoclonal antibodies, TSH-R antagonists, and other immunomodulatory agents show a promising outcome for GO patients.

Intraocular lens dislocation and tube shunt in the posterior chamber: a case report.

BACKGROUND: To describe management of a case of intraocular lens (IOL) and capsular bag (CB) dislocation in an eye with an Ahmed glaucoma valve in the posterior chamber. CASE PRESENTATION: A 75-year-old pseudophakic man with open-angle glaucoma and diabetic retinopathy developed neovascular glaucoma. After two intravitreous injections of bevacizumab and panretinal photocoagulation were administered, the new vessels regressed. However, goniosynechiae were observed over 360° of the angle. An Ahmed glaucoma valve model FP7 was implanted with the tube in the posterior chamber with adequate intraocular pressure control. Nineteen years after cataract surgery, when the IOL-CB complex became dislocated, they were sutured transclerally to the sulcus without Ahmed glaucoma valve modification. After a coughing episode, the vitreous pushed the IOL-CB complex forward and the tube was behind the IOL-CB complex. A 25-gauge posterior vitrectomy was performed, and the tube was returned to in front of the optic of the IOL using a forceps tip through a sclerotomy. CONCLUSION: This case suggested that management of IOL-CB dislocation can modify glaucoma shunt function. A complete pars plana vitrectomy may be required in order to reposition the dislocated IOL-CB complex in the presence of a posterior chamber drainage tube implant.

Evaluation of macular retinal ganglion cell-inner plexiform layer thickness after vitrectomy with internal limiting membrane peeling for idiopathic macular holes.

PURPOSE: To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness changes after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole repair using a high-resolution spectral-domain optical coherence tomography (SD-OCT). METHODS: 32 eyes from 32 patients with idiopathic macular holes who underwent vitrectomy with internal limiting membrane peeling between January 2011 and July 2012 were retrospectively analyzed. GCIPL thickness was measured before surgery, and at one month and at six months after surgery. Values obtained from automated and semimanual SD-OCT segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA). RESULTS: No significant differences were found between average GCIPL thickness values between preoperative and postoperative analysis. However, statistical significant differences were found in GCIPL thickness at the temporal macular quadrants at six months after surgery. Quality measurement analysis performed by automated segmentation revealed a significant number of segmentation errors. Semimanual segmentation slightly improved the quality of the results. CONCLUSION: SD-OCT analysis of GCIPL thickness found a significant reduction at the temporal macular quadrants at 6 months after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole.

Growth of geographic atrophy on fundus autofluorescence and polymorphisms of CFH, CFB, C3, FHR1-3, and ARMS2 in age-related macular degeneration.

IMPORTANCE: Identification of the genetic risk factors that contribute to geographic atrophy (GA) could lead to advancements in interventional trials and/or therapeutic approaches for combating vision loss. OBJECTIVE: To investigate whether single-nucleotide polymorphisms (SNPs) are associated with the presence and progression of established GA in age-related macular degeneration (AMD). DESIGN, SETTING, AND PARTICIPANTS: Prospective, controlled, multicenter study of 154 patients with GA/AMD and 141 age-matched control participants at 8 Spanish hospitals. MAIN OUTCOMES AND MEASURES: Samples of DNA were collected to analyze SNPs within AMD-related genes (CFH, CFB, C3, FHR1-3, and ARMS2). Fundus autofluorescence imaging was used to evaluate GA progression during a 2-year period in 73 patients with GA/AMD. Finally, logistic regression was used to analyze the associations of SNPs, age, body mass index, and cigarette smoking with the rate of progression and relative growth of GA. RESULTS: This case-control analysis revealed a significant (P < .05) association between the presence of GA and SNPs within CFH, ARMS2, and FHR1-3. Moreover, logistic regression analysis identified significant associations of the rate of progression with genetic polymorphisms (CFH-402His [P = .04] and CFH-62Ile [P = .04]) and demographic factors (sex [P = .02] and age [P = .02]), whereas relative growth was associated with 1 polymorphism (CFB-32Gln [P = .04]).Conclusions and Relevance Taken together, our findings confirm that genetic risk factors related to the presence of GA are not identical to those associated with GA progression. In fact, we demonstrate that gene variants of CFH and CFB, as well as demographic risk factors, confer significant risk for GA progression (both rate of progression and relative growth) within a Spanish population.