PURPOSE: To determine whether the blue arc entoptic phenomenon, a positive visual response originating from the retina with a shape that conforms to the topology of the nerve fiber layer, is depressed in glaucoma. METHODS: We recruited a cross-sectional, nonconsecutive sample of 202 patients from a single institution in a prospective manner. Subjects underwent full ophthalmic examination, including standard automated perimetry (Humphrey Visual Field 24-2) or frequency doubling technology (Screening C 20-5) perimetry. Eligible patients viewed computer-generated stimuli under conditions chosen to optimize perception of the blue arcs. Unmasked testers instructed patients to report whether they were able to perceive blue arcs but did not reveal what response was expected. We created multivariable logistic regression models to ascertain the demographic and clinical parameters associated with perceiving the blue arcs. RESULTS: In multivariable analyses, each 0.1 unit increase in cup-disc ratio was associated with 36% reduced likelihood of perceiving the blue arcs (odds ratio [OR] = 0.66 [95% confidence interval (CI): 0.53-0.83], P<.001). A smaller mean defect was associated with an increased likelihood of perceiving the blue arcs (OR=1.79 [95% CI: 1.40-2.28]); P<.001), while larger pattern standard deviation (OR=0.72 [95% CI: 0.57-0.91]; P=.005) and abnormal glaucoma hemifield test (OR=0.25 [0.10-0.65]; P=.006) were associated with a reduced likelihood of perceiving them. Older age and media opacity were also associated with an inability to perceive the blue arcs. CONCLUSION: In this study, the inability to perceive the blue arcs correlated with structural and functional features associated with glaucoma, although older age and media opacity were also predictors of this entoptic response.
Corneal transplantation is the most commonly performed organ transplantation. Immune privilege of the cornea is widely recognized, partly because of the relatively favorable outcome of corneal grafts. The first-time recipient of corneal allografts in an avascular, low-risk setting can expect a 90% success rate without systemic immunosuppressive agents and histocompatibility matching. However, immunologic rejection remains the major cause of graft failure, particularly in patients with a high risk for rejection. Corticosteroids remain the first-line therapy for the prevention and treatment of immune rejection. However, current pharmacological measures are limited in their side-effect profiles, repeated application, lack of targeted response, and short duration of action. Experimental ocular gene therapy may thus present new horizons in immunomodulation. From efficient viral vectors to sustainable alternative splicing, we discuss the progress of gene therapy in promoting graft survival and postulate further avenues for gene-mediated prevention of allogeneic graft rejection.
PURPOSE: Dry eye disease affects women twice as often as men, but there is little information on whether dry eye treatments, treatment satisfaction, or the impact of dry eye disease on patients' lives and vision might differ by sex. DESIGN: Questionnaire survey of 4000 participants in the Women's Health Study and the Physicians' Health Studies I and II with a prior report of a diagnosis of DED. METHODS: Among participants who re-confirmed a diagnosis of dry eye disease, we assessed symptoms, treatments, patient satisfaction and impact of dry eye disease, and analyzed differences between men and women using regression models. RESULTS: The final study population consisted of 1,518 women (mean age 70.7 years) and 581 men (mean age 76.7 years), with a mean reported duration of dry eye disease of 10.5 years and 10.1 years, respectively. The frequency and severity of dry eye disease symptoms were higher among women (each P<0.0001), and women reported a greater impact on everyday activities (P<0.0001). Women were more likely to use artificial tears (P<0.0001) use them more often (P<0.0001), and to use Restasis® (P<0.0001), omega-3 fatty acids (P=0.0006), and have punctal occlusion (P=0.005). Women spent more money per month on dry eye treatments (P<0.0001), but reported greater dissatisfaction with treatment side effects (P=0.001), and the amount of time before treatments started working (P=0.03). CONCLUSIONS: These data show that dry eye disease is generally experienced as being more severe among women, having a greater impact on their self-assessed well-being.
The Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive condition comprising nine genetically heterogeneous entities that feature oculocutaneous albinism (OCA) and bleeding tendency as their principal clinical manifestations. The pathogenesis of HPS involves disturbances in the biogenesis and trafficking of lysosome-related organelles. While the ophthalmologist is trained to address the ocular manifestations of OCA, it is critical for the provider to consider HPS when examining OCA patients as its systemic sequelae may be associated with morbidity and mortality. If there is suspicion of HPS in a patient with albinism, the ophthalmologist should enlist the aid of consultants to confirm the diagnosis and monitor for systemic features. As the nine HPS subtypes explored in this article vary widely in the character and severity of their associated systemic manifestations, some authors advocate determining the specific gene defect in each HPS patient in order to optimize care and provide anticipatory guidance.
Uveal melanoma (UM) has a strong propensity to metastasize and the prognosis for metastatic disease is very poor. It has been suggested that occult micrometastases are already present, but undetectable, in many patients at the time when the primary ocular tumor is diagnosed and treated. To identify high-risk patients for close monitoring and early intervention with prophylactic adjuvant systemic therapy, an accurate predictive system is necessary for stratifying those patients at risk of developing metastatic disease. To date, many clinical and histopathological features, molecular pathway characteristics, and genetic fingerprints of UM have been suggested for disease prognostication. Among the newest of them, tumor genetics has received the most attention in demonstrating promise as a prognostic tool. Because of the plethora of recent developments, we summarize and compare in this review the important standard and more advanced cytogenetic prognostic markers. We further describe the variety of genetic tests available for prognostication of UM, and provide a critical assessment of the respective advantages and disadvantages of these tools.
Primary open-angle glaucoma (POAG) is a common disease with complex inheritance. The identification of genes predisposing to POAG is an important step toward the development of novel gene-based methods of diagnosis and treatment. Genome-wide association studies (GWAS) have successfully identified genes contributing to complex traits such as POAG however, such studies frequently require very large sample sizes, and thus, collaborations and consortia have been of critical importance for the GWAS approach. In this report we describe the formation of the NEIGHBOR consortium, the harmonized case control definitions used for a POAG GWAS, the clinical features of the cases and controls, and the rationale for the GWAS study design.
PURPOSE: Vascular anomalies comprise malformations, hemangiomas, and rare tumors. The commonality among these lesions is their origin in vascular endothelia. Most occur sporadically, but occasional inheritance is observed and thus allows genetic research and insight into etiology. This review highlights those vascular anomalies in which genetic inheritance has been demonstrated. METHODS: A comprehensive literature search was performed on PubMed. Fifty-five full-length articles were reviewed. RESULTS: Five categories of vascular anomalies with patterned inheritance were identified: arteriovenous malformation (AVM), capillary malformation (CM), lymphatic malformation (LM), venous malformation (VM), and infantile hemangioma (IH). Capillary and arteriovenous malformation subtypes are associated with a RASA-1 gene mutation and show autosomal dominant inheritance. VEGFR3 mutations have been associated with generalized forms of LM and lymphedema. Mutations in TIE2/TEK genes cause inherited forms of venous malformations also with autosomal dominant inheritance. Familial clustering and atopic disease are associated with infantile hemangioma, and gene expression varies with the developmental stage of these lesions. CONCLUSION: Most vascular anomalies occur sporadically, but several genes and genetic disorders have been associated with them. Specific forms of capillary malformation appear to be most convincingly associated with genomic errors. Further research promises new insights into the development of this diverse group of disorders.
OBJECTIVE: To compare functional and anatomical outcomes after idiopathic epiretinal membrane (ERM) peeling combined with phacoemulsification and intraocular lens implantation versus ERM peeling alone. METHODS: A retrospective, non-randomised comparative case series study was conducted of 81 eyes from 79 patients who underwent ERM peeling at the Beth Israel Deaconess Medical Center between 2001 and 2010. Eyes that underwent combined surgery for ERM and cataracts (group 1) were compared with those that had ERM peeling alone (group 2) with respect to best-corrected visual acuity at 6 months and 1 year after surgery, postoperative central macular thickness (CMT) as measured on optical coherence tomography, and rates of complications, including elevated intraocular pressure (IOP), ERM recurrence and need for reoperation. RESULTS: Mean logMAR visual acuity improved significantly in both groups at 6 months (p<0.001) and 1 year (p<0.001) after surgery. There was no statistical difference between the two groups in visual acuity improvement at 6 months (p=0.108) or 1 year (p=0.094). Mean CMT of both groups also significantly decreased after surgery (p=0.002), with no statistical difference in CMT reduction between the two groups, but a trend toward less CMT reduction in group 1 (p=0.061). The rates of complications, including IOP elevation, ERM recurrence and frequency of reoperation, were similar in the two groups, with non-statistical trends toward greater ERM recurrence (p=0.084) and need for reoperation (p=0.096) in those that had combined surgery. CONCLUSIONS: Combined surgery for ERMs and cataracts may potentially be as effective as membrane peeling alone with respect to visual and anatomical outcomes. Further studies are necessary to determine if there may be greater ERM recurrence or need for reoperation after combined surgery.