Novel stem cell and gene therapy in diabetic retinopathy, age related macular degeneration, and retinitis pigmentosa.

Degenerative retinal disease leads to significant visual morbidity worldwide. Diabetic retinopathy and macular degeneration are leading causes of blindness in the developed world. While current therapies for these diseases slow disease progression, stem cell and gene therapy may also reverse the effects of these, and other, degenerative retinal conditions. Novel therapies being investigated include the use of various types of stem cells in the regeneration of atrophic or damaged retinal tissue, the prolonged administration of neurotrophic factors and/or drug delivery, immunomodulation, as well as the replacement of mutant genes, and immunomodulation through viral vector delivery. This review will update the reader on aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa and other less common inherited retinal dystrophies. These therapies include the use of adeno-associated viral vector-based therapies for treatment of various types of retinitis pigmentosa and dry age-related macular degeneration. Other potential therapies reviewed include the use of mesenchymal stem cells in local immunomodulation, and the use of stem cells in generating structures like three-dimensional retinal sheets for transplantation into degenerative retinas. Finally, aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and other less common inherited retinal dystrophies will be reviewed.

Development of Monofixation Syndrome After Extraction of Dense Cataracts.

PURPOSE: If the interruption of macular fusion for an extended period of time is the key event that results in the development of monofixation syndrome, then the decreased macular input caused by dense cataracts may cause monofixation syndrome in adults. This study was designed to test this hypothesis. METHODS: The study design was a retrospective chart review that identified patients with unilateral cataracts at two southern Louisiana medical centers. Patients were assigned to the dense cataract group if a unilateral cataract had been present for at least 3 months and led to a visual acuity of worse than 20/200. Patients in the control group had a unilateral cataract for more than 3 months and visual acuity better than 20/200 in the affected eye. Stereoacuity was assessed using the Titmus or Randot stereo test. A Worth 4-dot test viewed at a distance of 20 feet was used to assess the presence of a macular scotoma. The criteria for monofixation syndrome were met if stereoacuity was less than 60 seconds and the Worth 4-dot test demonstrated central macular scotoma at 20 feet. RESULTS: The dense cataract group's association with monofixation syndrome was statistically significant when compared to the control group (P < .0001). CONCLUSIONS: This study adds dense adult-onset cataracts to the list of causes of monofixation syndrome and reduced stereoacuity. A delay in treating dense lens opacities can result in good visual outcome but an inferior binocular visual outcome (poor stereoacuity). [J Pediatr Ophthalmol Strabismus. 2017;54(1):39-42.].

Rates of Reoperation and Abnormal Binocularity Following Strabismus Surgery in Children.

PURPOSE: To determine predictors of reoperation and abnormal binocularity outcomes (including amblyopia and diplopia) following pediatric strabismus surgery. DESIGN: Retrospective cross-sectional study. METHODS: setting: Review of a national insurance database. STUDY POPULATION: Children under age 18 years having strabismus procedures between 2007 and 2013. INTERVENTIONS: Adjustable- or fixed-suture strabismus surgery, or botulinum toxin injection. OUTCOME MEASURES: Reoperation or diagnosis of abnormal binocularity in the first postoperative year. RESULTS: Of 11 115 children having strabismus procedures, 851 (7.7%) underwent reoperation. The reoperation rate was 7.4% for fixed-suture surgeries, 9.6% for adjustable-suture surgeries (P = .18), and 44.9% for botulinum injections (P < .001). Age under 2 years was associated with higher reoperation and abnormal binocularity rates (P < .001). For horizontal strabismus, the postoperative abnormal binocularity rate was 12.8% for fixed-suture surgery and 26.5% for botulinum injection (P = .005). Reoperation rates tended to be higher with adjustable sutures (odds ratio [OR] 1.69, 95% confidence interval [CI] 0.94-3.03, P = .08) or botulinum toxin injection (OR 10.36, 95% CI 5.75-18.66, P < .001) and lower with 3- or 4-muscle surgery (P = .001). Esotropia, hyperopia, and botulinum injection were independently associated with higher rates of postoperative abnormal binocularity (P ≤ .005). For vertical surgeries, predictors of reoperation were adjustable-suture use (OR 2.51, P = .10) and superior oblique surgery (OR 2.36, P < .001). CONCLUSIONS: Adjustable sutures were not associated with a lower reoperation rate in children. Younger age, esotropia, hyperopia, and botulinum injection were associated with postoperative abnormal binocularity. Superior oblique surgery and botulinum injection were associated with higher rates of reoperation.

Cigarette smoking and male sex are independent and age concomitant risk factors for the development of ocular sarcoidosis in a New Orleans sarcoidosis population.

INTRODUCTION: Sarcoidosis is a multi-organ system granulomatous disease of unknown origin with an incidence of 1-40/100,000. Though pulmonary manifestations are predominant, ocular sarcoidosis (OS) affects 25-50% of patients with sarcoidosis and can lead to blindness. METHODS: A retrospective, single-center chart review of sarcoidosis cases investigated variables associated with the development of OS. Inclusion criteria were biopsy-proven sarcoidosis, disease duration greater than 1 year, documented smoking status on chart review and documentation of sarcoid-related eye disease. Multivariate analysis identified independent risk factors for OS. RESULTS: Of 269 charts reviewed, 109 patients met inclusion criteria. The OS group had a significantly higher proportion of smokers (71.4%) than without OS (42.0%, p=0.027) with no difference (p=0.61) in median number of pack years. Male sex was significantly higher in the OS group (57.1% versus 26.1%, p=0.009). Median duration of sarcoidosis was higher in the OS group (10 versus 4 years, p=0.031). Multivariate regression identified tobacco exposure (OR=5.25, p=0.007, 95% CI 1.58-17.41), male sex (OR=7.48, p=0.002, 95% CI 2.15-26.01), and age (OR=1.114, p=0.002, 95% CI 1.04-1.19) as concomitant risk factors for the development of OS. CONCLUSION: To date, there are few dedicated investigations of risk factors for OS, especially smoking. This investigation identified male sex, age, and tobacco exposure as independent risk factors for OS. Though disease duration did not withstand regression analysis in this moderately sized group, age at chart review suggests screening for OS should not remit but rather intensify in aging patients with sarcoidosis.