In 1994, The American Journal of Pathology published a key article reporting that hypoxic retina produces vascular endothelial growth factor (VEGF), suggesting a role for VEGF in ocular neovascularization. Subsequent developments in anti-VEGF treatment for neovascular eye disease have improved visual outcomes and changed the standard of care in retinal medicine and ophthalmology.
PURPOSE: The purpose of this study was to investigate the presence of progenitor cells in the uninjured, adult rat lacrimal gland (LG). METHODS: The presence of progenitor cells was examined in LG sections from male rats using antibodies against selected stem cell markers and α-smooth muscle actin (SMA), which marks myoepithelial cells (MECs), by immunofluorescence microscopy (IF). Small, immature cells were isolated after digestion of LG with collagenase and culture in RPMI 1640 for 2 weeks. Immature cells were examined for expression of stem cell markers by IF. Immature cell were grown in neuronal, epithelial, and myoepithelial cell media, and examined by light morphology and IF using antibodies to markers of different cell lineages. RESULTS: In the intact LGs, MECs expressed the stem cell markers nestin, Musashi 1, ABCG2, Pax6, Chx 10, ΔN p63, and Sox 2. All markers colocalized with SMA. Isolated immature cells contained Ki-67, nestin, Musashi 1, Pax 6, and CHX 10. In neuronal media, immature cells differentiated and assumed a neuronal cell morphology expressing neurofilament 200. In media for human corneal endothelial cells, immature cells differentiated, assumed cobblestone morphology, and labeled with the epithelial marker AE1/AE3. In RPMI media immature cells differentiated into cells with MEC-like morphology, and expressed the MEC markers SMA, α-actinin, adenylate cyclase II, and vimentin. CONCLUSIONS: We conclude that uninjured, adult LG contains progenitor cells that may be MECs, which can be isolated and differentiated into multiple lineages.
The authors demonstrate a reproducible technique using processed pericardium to seal sclerostomy track during glaucoma shunt revision. The suggested method involves placement of a wedge-shaped processed pericardial graft into the old sclerostomy tract following tube explantation. The graft is trimmed and sutured to the sclera. The tube is reinserted into a new sclerostomy and then sutured in place and covered in the usual fashion. This method allowed relatively easy treatment of three patients with patulous sclerostomy with necrotic edges. A successful tube revision and repositioning of the tube using this technique was performed on three patients with exposed tubes. The intraocular pressure was between 8 and 12 mm Hg from postoperative day 1. The authors suggest the use of pericardium plug to adequately seal the old sclerostomy track during glaucoma shunt revision. The plug allows tube repositioning at a new site without the need to suture the friable sclerostomy edges.
PURPOSE: To report ocular injuries caused by airsoft guns in children. METHODS: A retrospective chart review of pediatric patients who sustained ocular injuries related to airsoft guns between November 2005 and December 2007. Place of trauma, presenting symptoms and signs, surgical interventions performed, and final visual outcome were reviewed. RESULTS: Thirty-two patients with a mean age of 8.8 ± 4.0 years (range: 1.5 to 18 years) were examined; 28 were boys (87.5%). Presenting visual acuity ranged from hand motions to 20/20 and could not be assessed in 2 patients. Hyphema was a common finding that was present in 24 cases, corneal abrasions were present in 10 cases, and raised intraocular pressure was present in 7 cases. Seven patients presented with traumatic cataract, and two had iridodialysis. Immediate surgical intervention was performed in 7 patients and 7 patients were scheduled for elective surgery. The patients presented after an average of 1.9 ± 1.9 days (range: 4 hours to 6 days) after the injury. Average follow-up was 18 days (range: 7 days to 5 months). Final visual acuity was 20/200 or worse in 5 patients, 20/40 or better in 23 patients, and could not be assessed in 2 cases. CONCLUSION: Airsoft guns can cause a variety of serious injuries, sometimes necessitating operative intervention. The long-term morbidity from some of these injuries is significant. Airsoft guns are capable of inflicting serious and permanent ocular damage.
PURPOSE: To determine if central corneal thickness (CCT) impacts the intraocular pressure (IOP)-lowering effect of selective laser trabeculoplasty (SLT) in patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG). METHODS: A retrospective chart review of consecutive patients, who underwent SLT as primary treatment for OHT and POAG, between 2002 and 2005, was performed. Partial correlation analysis was performed to correlate the CCT to the percentage of IOP reduction at 3 to 30 months after SLT. Independent samples t test was performed to compare mean percentage of IOP reduction in eyes with CCT less than 555 μm versus CCT 555 μm or greater. RESULTS: Eighty eyes of 47 patients were identified. The partial correlation coefficient value between the CCT and percentage of IOP reduction after SLT at 3 months was -0.253 (P = 0.025), at 12 months it was -0.22 (P = 0.049), and at 30 months it was 0.301 (P = 0.007). Independent samples t test showed that the mean percentage of IOP reduction in eyes with thinner corneas (CCT < 555 μm) was greater than that in thicker corneas (CCT ≥ 555 μm) at 3-, 6-, 9-, 12-, and 30-month post-SLT (P < 0.05). CONCLUSIONS: In patients with POAG and OHT, percentage of IOP reduction after SLT was significantly greater in eyes with thinner corneas (CCT < 555 μm). These findings indicate that patients treated with SLT as primary therapy who had thinner corneas demonstrated better IOP control for at least 30 months after SLT.
In vivo confocal microscopy (IVCM) of the cornea is becoming an indispensable tool in the cellular study of corneal physiology and disease. This technique offers non-invasive imaging of the living cornea with images comparable to that of ex vivo histology. The ability to provide high-resolution images of all layers in the living cornea has resulted in new discoveries of corneal pathology at the cellular level. The IVCM analysis of corneal dystrophies is of importance to clinicians, as current methods of diagnosis involve slit-lamp characteristics, genetic analysis, and invasive biopsy. IVCM is helpful in evaluating the morphological characteristics of corneal dystrophies at the histological level and may be helpful in diagnosis, determination of progression, and understanding the pathophysiology of disease. The purpose of this review is to describe the principles, applications, and clinical correlation of IVCM in the study of corneal dystrophies.
PURPOSE: To compare nonmydriatic stereoscopic Optomap ultrawide field images with dilated stereoscopic Early Treatment Diabetic Retinopathy Study 7-standard field 35-mm color 30-degree fundus photographs (ETDRS photography) and clinical examination for determining diabetic retinopathy (DR) and diabetic macular edema (DME) severity. DESIGN: Single-site, prospective, comparative, instrument validation study. METHODS: One hundred three diabetic patients (206 eyes) representing the full spectrum of DR severity underwent nonmydriatic ultrawide field 100-degree and 200-degree imaging, dilated ETDRS photography, and dilated fundus examination by a retina specialist. Two independent readers graded images to determine DR and DME severity. A third masked retina specialist adjudicated discrepancies. RESULTS: Based on ETDRS photography (n = 200), the results were as follows: no DR (n = 25 eyes [12.5%]), mild nonproliferative DR (NPDR; 47 [23.5%]), moderate NPDR (61 [30.5%]), severe NPDR (11 [5.5%]), very severe NPDR (3 [1.5%]), and proliferative DR (52 [2.5%]). One (0.5%) eye was ungradable and 6 eyes did not complete ETDRS photography. No DME was found in 114 eyes (57.0%), DME was found in 28 eyes (14.0%), and clinically significant DME was found in 47 eyes (23.5%), and 11 (5.5%) eyes were ungradable. Exact DR severity agreement between ultrawide field 100-degree imaging and ETDRS photography occurred in 84%, with agreement within 1 level in 91% (K(W) = 0.85; K = 0.79). Nonmydriatic ultrawide field images exactly matched clinical examination results for DR in 70% and were within 1 level in 93% (K(W) = 0.71; K = 0.61). Nonmydriatic ultrawide field imaging acquisition time was less than half that of dilated ETDRS photography (P < .0001). CONCLUSIONS: Nonmydriatic ultrawide field images compare favorably with dilated ETDRS photography and dilated fundus examination in determining DR and DME severity; however, they are acquired more rapidly. If confirmed in broader diabetic populations, nonmydriatic ultrawide field imaging may prove to be beneficial in DR evaluation in research and clinical settings.
The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences with identical hexon genes, which were the same as the one previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusive reliance on serum neutralization can lead to mischaracterization of adenoviruses and miss coinfections. Whole-genome sequencing remains the gold standard for proper classification of HAdVs.
Sobrin L, Ripke S, Yu Y, Fagerness J, Bhangale T, Tan P, Souied E, Buitendijk G, Merriam J, Richardson A, Raychaudhuri S, Reynolds R, Chin K, Lee A, Leveziel N, Zack D, Campochiaro P, Smith T, Barile G, Hogg R, Chakravarthy U, Behrens T, Uitterlinden A, Duijn C, Vingerling J, Brantley M, Baird P, Klaver C, Allikmets R, Katsanis N, Graham R, Ioannidis J, Daly M, Seddon J. Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes. Ophthalmology. 2012;119(9):1874–85.
PURPOSE: To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes. DESIGN: Sibling correlation study and genome-wide association study (GWAS). PARTICIPANTS: For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls. METHODS: Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts. MAIN OUTCOME MEASURES: Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes. RESULTS: The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree (P = 4.2 × 10(-5)), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3 × 10(-9)), which was confirmed in the replication samples (OR, 1.38; P = 7.4 × 10(-14) for combined discovery and replication analysis). CONCLUSIONS: Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies.