Histopathology of Age-Related Macular Degeneration and Implications for Pathogenesis and Therapy.

Aging is associated with a number of histological changes in the choroid, Bruch's membrane, RPE, and neuroretina. Outside of the normal physiologic aging spectrum of changes, abnormal deposits such as basal laminar deposits, basal linear deposits, and soft drusen are known to be associated with AMD. Progression of AMD to advanced stages involving geographic atrophy, choroidal neovascularization, and/or disciform scars can result in debilitating vision loss. Knowledge of the angiogenic pathway and its components that stimulate neovascularization has led to the development of a new paradigm of intravitreal anti-VEGF pharmacotherapy in the management of neovascular AMD. Currently however, there are no available treatments for the modification of disease progression in non-neovascular AMD, or for the treatment of geographic atrophy. Further understanding of the histopathology of AMD and the molecular mechanisms that contribute to pathogenesis of the disease may reveal additional therapeutic targets.

Evaluation of Potential Systemic Adverse Events Related to Fluorescein Angiography in Pediatric Patients.

PURPOSE: To evaluate adverse events of fluorescein angiography (FA) in pediatric patients. DESIGN: Single-institution retrospective chart review. PARTICIPANTS: Patients 0 to 18 years of age who underwent FA between January 2010 and December 2015 at a single institution in the United States. METHODS: Pediatric patients who underwent FA by 3 surgeons were included in the study. Patients with fewer than 24 hours of documented follow-up were excluded. Significant adverse events within 24 hours of FA were evaluated. Detailed intraoperative and perioperative physiological parameters, including heart rate, blood pressure, oxygen saturation, and ventilation parameters, in inpatients undergoing simultaneous examination under anesthesia were reviewed. Peri-injection effects of FA were evaluated by 2-tailed paired t test comparison of mean 5-minute preinjection and 5-minute postinjection physiological data. MAIN OUTCOME MEASURES: Significant adverse events associated with FA. RESULTS: One hundred fifteen patients with a total of 214 FA examinations were included. No significant adverse events were associated directly with FA. Comparison of mean 5-minute preinjection and postinjection physiologic parameters in 27 patients who underwent intravenous FA during EUA did not reveal significant changes associated with FA. A significant difference was found in average patient age between inpatient (2.5 years) and outpatient (10.7 years) FA (P < 0.00001). The youngest patients who underwent successful FA were 3.8 years old in the outpatient setting and 32 weeks' postmenstrual age in the inpatient setting. Patients younger than 3.8 years accounted for most (77.6%; n = 85) inpatient FA examinations. Excluding patients with a need or likely need for laser or surgery, the reasons for inpatient FA in patients older than 3.8 years included the lack of availability of outpatient ultra-widefield FA (UWFA) and more challenging situations in patients with developmental delay. CONCLUSIONS: Fluorescein angiography was not found to be associated directly with systemic adverse events in pediatric patients in this study. Younger patients more commonly were found to require an inpatient FA, whereas older patients older than 4 years underwent outpatient UWFA.

Surgical Management of an Externally Protruding, Perforating Intraocular Foreign Body.

Ru-ik Chee Felix Y. Chau In this case of a perforating eye injury by a 2-inch-long nail that went through the cornea, lens, and posterior eye wall, the authors describe a combined external, anterior, and posterior segment surgical approach that resulted in safe and successful removal of the foreign body. Initial external trimming of the protruding nail facilitated the use of a noncontact viewing system. Combined limbal and pars plana placement of the vitrectomy cannulas optimized access to both anterior and posterior intraocular structures. Most importantly, careful removal of potential sources of foreign body adhesion to intraocular structures prior to extraction likely increased the likelihood for a successful clinical outcome. Care was taken to remove as much of the vitreous as possible and to keep the eye formed. The patient recovered 20/25+2 vision with aphakic correction.

Retinal Telemedicine.

PURPOSE OF REVIEW: An update and overview of the literature on current telemedicine applications in retina. RECENT FINDINGS: The application of telemedicine to the field of Ophthalmology and Retina has been growing with advancing technologies in ophthalmic imaging. Retinal telemedicine has been most commonly applied to diabetic retinopathy and retinopathy of prematurity in adult and pediatric patients respectively. Telemedicine has the potential to alleviate the growing demand for clinical evaluation of retinal diseases. Subsequently, automated image analysis and deep learning systems may facilitate efficient processing of large, increasing numbers of images generated in telemedicine systems. Telemedicine may additionally improve access to education and standardized training through tele-education systems. SUMMARY: Telemedicine has the potential to be utilized as a useful adjunct but not a complete replacement for physical clinical examinations. Retinal telemedicine programs should be carefully and appropriately integrated into current clinical systems.

Anti-Vascular Endothelial Growth Factor and the Evolving Management Paradigm for Retinopathy of Prematurity.

Diagnosis and management of pediatric retinal conditions such as retinopathy of prematurity (ROP) have been evolving significantly with the availability of new technology and treatments. New imaging systems, telemedicine, tele-education, and anti‒vascular endothelial growth factor (VEGF) intravitreal pharmacotherapy are all changing the way we diagnose and deliver care to children with pediatric retinal disease. Fluorescein angiography and optical coherence tomography have the potential to improve our diagnosis and management of disease, and with improvements in retinal imaging, telemedicine is becoming more feasible. Telemedicine, tele-education, and computer-based image analysis may overcome many of the challenges we face in providing adequate care and access for children with pediatric retinal disease. Treatment options have also expanded with the use of anti-VEGF therapy. Although the use of intravitreal anti-VEGF for ROP has been documented in the literature for more than a decade, many questions still remain about its safety in the pediatric patient population. Several ongoing prospective studies are exploring the utility of anti-VEGF agents for ROP, with attention to the optimal dose of drug, systemic safety, and our understanding of recurrence of disease. This review aims to provide an update on current diagnostic and therapeutic modalities, focusing predominantly on the role of anti-VEGF therapy, for the management of ROP and other pediatric retinal vascular diseases.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN MACULA-INVOLVING CYTOMEGALOVIRUS RETINITIS.

PURPOSE: To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). METHODS: Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis. RESULTS: Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole-associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis. CONCLUSION: Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.

Ocular Decompression Retinopathy After Uncomplicated Cataract Surgery in a Patient With a History of Narrow-Angle Glaucoma.

PURPOSE: To describe a case of ocular decompression retinopathy following uncomplicated cataract surgery in a patient with phacomorphic narrow-angle glaucoma. METHODS: Case report with wide-field fundus imaging. RESULTS: A 57-year-old woman with a history of phacomorphic narrow-angle glaucoma presented 1 day after uncomplicated cataract extraction with intraocular lens insertion of the left eye with hand motion vision. She was found to have decompression retinopathy with large prefoveal subhyaloid hemorrhage. The hemorrhages gradually improved over time with observation. CONCLUSIONS: We report a case of decompression retinopathy after uncomplicated cataract extraction in a patient with phacomorphic narrow-angle glaucoma. This report expands upon the procedures after which decompression retinopathy has been diagnosed and suggests a need for careful perioperative management in patients with glaucoma.

LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis.

The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenish the stemness capacity has been stalled by the lack of reliable corneal epithelial stem cell markers. Here we identified the location of Lhx2 in mice (mLhx2) cornea and conjunctival tissue using an Lhx2eGFP reporter model and in human tissues (hLHX2). Lhx2 localized to the basal cells of central cornea, the conjunctiva and the entire limbal epithelium in humans and mice. To ascribe a functional role we generated Lhx2 conditional knockout (cKO) mice and the phenotypic effects in corneas were analyzed by slit lamp microscopy, in cell-based assays and in a model of corneal epithelium debridement. Immunodetection on corneal sections were used to visualize conjunctivalization, a sign of limbal barrier failure. Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification. Cell based assays showed that Lhx2cKO derived corneal epithelial cells have a significantly lower capacity to form colonies over time and delayed wound-healing recovery when compared to wildtype cells. Repeated corneal epithelial wounding resulted in decreased re-epithelialization and multiple cornea lesions in Lhx2cKO mice compared to normal recovery seen in wildtype mice. We conclude that Lhx2 is required for maintenance of the corneal epithelial cell compartment and the limbal barrier.

Association of blood and ocular perfusion pressure with structural glaucomatous progression by flicker chronoscopy.

BACKGROUND: Vascular risk factors have been associated with glaucomatous visual field progression. AIM: We determined the relationship between vascular risk factors and structural glaucomatous progression using serial flicker chronoscopy images. METHODS: Two glaucoma fellowship-trained ophthalmologists, masked to temporal sequence, independently graded serial flicker chronoscopy images from one eye of a cohort of glaucoma patients for features of structural progression in this retrospective cohort study. After adjudication, simple and multiple logistic models were constructed to determine variables associated with increased odds of progression, including systolic blood pressure (BP), diastolic BP and mean ocular perfusion pressure. RESULTS: Seventy-two eyes of 72 patients were analysed. Patients with any form of structural progression (n=40) were older (67.0 vs 58.8 years; p=0.005) and had lower diastolic BP (71.8 vs 76.5 mm Hg; p=0.02) than patients without progression (n=32). In the univariable model, diastolic BP was associated with progressive retinal nerve fibre layer (RNFL) loss (OR=0.2 per 10 mm Hg, 95% CI 0.1 to 0.6, p<0.006) and neuroretinal rim loss (OR=0.4 per 10 mm Hg, 95% CI 0.2 to 0.8, p<0.01). Diastolic BP was also significant in the multivariable model for RNFL loss (p=0.009) and neuroretinal rim loss (p=0.003). CONCLUSIONS: This study is the first to use structural progression and flicker chronoscopy to identify vascular glaucoma risk factors. Older age and lower diastolic BP were associated with progression. By multivariable analysis diastolic BP was associated with RNFL and neuroretinal rim loss. These findings suggest that diastolic BP is associated with structural glaucomatous progression which may have implications for management.

Agreement of flicker chronoscopy for structural glaucomatous progression detection and factors associated with progression.

PURPOSE: To evaluate agreement of flicker chronoscopy for structural glaucomatous progression detection and factors associated with progression. DESIGN: Retrospective cohort study. METHODS: Two glaucoma fellowship-trained ophthalmologists, masked to temporal sequence, independently graded serial flicker chronoscopy images from 1 eye of a cohort of glaucoma patients for features of structural progression. Agreement between graders was determined, as was accuracy for determining the temporal order of images. After adjudication, simple and multiple logistic models were constructed to determine baseline variables associated with increased odds of progression. RESULTS: Fifty of 103 included eyes/patients (48.5%) had at least 1 sign of structural progression. Temporal sequence was incorrectly determined in 14 of 206 cases (6.4%). Interobserver agreements for identifying baseline photographs (κ = 0.9), global progression (κ = 0.7), parapapillary atrophy (PPA) progression (κ = 0.7), disc hemorrhages (κ = 0.7), neuroretinal rim loss (κ = 0.5), and retinal nerve fiber layer (RNFL) loss (κ = 0.2) were calculated. Age was significantly associated with global (1.8; 1.3-2.6, P < .001) (odds ratio; 95% confidence interval, significance) and PPA progression (1.7; 1.2-2.4, P = .002). Lower corneal hysteresis was associated with global progression (0.78; 0.56-0.99, P = .049) and RNFL loss (0.5; 0.3-0.9, P = .02). Goldmann-correlated intraocular pressure (1.0, 0.7-1.4, P = .9), visual field mean deviation (1.0, 0.9-1.0, P = .2), and central corneal thickness (0.9, 0.8-1.0, P = .1) were not significantly associated with progression. On multivariable analysis, only age was associated with global progression (1.8; 1.2-2.5, P = .002). CONCLUSION: Flicker chronoscopy demonstrated acceptable interobserver agreement in structural progression detection. Corneal hysteresis and age were both associated with progression, but age was the only significant factor on multivariable analysis.

Allergic fungal sinusitis causing nasolacrimal duct obstruction.

INTRODUCTION: Allergic fungal sinusitis is thought to represent a chronic autoimmune reaction directed against fungal elements within the sinuses, and is commonly seen in individuals with a history of chronic sinusitis that is refractory to medical therapy. The authors present a case of allergic fungal sinusitis involving the lacrimal drainage system. CASE: A 54-year-old woman initially presented with recurrent erythema and induration of the left nasolacrimal sac due to dacryocystitis, which was unresponsive to treatment with topical and systemic antibiotics. Radiological evaluation demonstrated the presence of multiple soft tissue masses along the medial canthi. During subsequent endoscopic dacryocystorhinostomy, significant amounts of allergic mucin were found within the sinuses and marked eosinophilia was present within tissue obtained from the lacrimal sac, findings highly suggestive of allergic fungal sinusitis. CONCLUSION: A diagnosis of allergic fungal sinusitis should be considered in patients presenting with epiphora in the appropriate clinical context. However, involvement of the lacrimal drainage system is an exceedingly unusual presentation.