RESUMO
Retinal pigmented epithelium (RPE) secretes transforming growth factor beta 1 and 2 (TGF-ß1 and -ß2) cytokines involved in fibrosis, immune privilege, and proliferative vitreoretinopathy (PVR). Since RPE cell polarity may be altered in various disease conditions including PVR and age-related macular degeneration, we determined levels of TGF-ß from polarized human RPE (hRPE) and human stem cell derived RPE (hESC-RPE) as compared to nonpolarized cells. TGF-ß2 was the predominant isoform in all cell culture conditions. Nonpolarized cells secreted significantly more TGF-ß2 supporting the contention that loss of polarity of RPE in PVR leads to rise of intravitreal TGF-ß2. Active TGF-ß2, secreted mainly from apical side of polarized RPE, represented 6-10% of total TGF-ß2. In conclusion, polarity is an important determinant of TGF-ß2 secretion in RPE. Low levels of apically secreted active TGF-ß2 may play a role in the normal physiology of the subretinal space. Comparable secretion of TGF-ß from polarized hESC-RPE and hRPE supports the potential for hESC-RPE in RPE replacement therapies.
Assuntos
Retina/citologia , Epitélio Pigmentado da Retina/citologia , Células-Tronco/citologia , Fator de Crescimento Transformador beta2/metabolismo , Transplante de Células , Células Cultivadas , Células-Tronco Embrionárias/citologia , Humanos , Isoformas de Proteínas/metabolismo , Retina/imunologia , Fator de Crescimento Transformador beta1/metabolismo , Vitreorretinopatia Proliferativa/patologiaRESUMO
Purpose: To provide extended safety and effectiveness follow-up for eyes treated with circumferential canaloplasty and trabeculotomy (CP+TR) that were included in the 12-month ROMEO study. Setting: Seven multi-subspecialty ophthalmology practices located in 6 states (Arkansas, California, Kansas, Louisiana, Missouri, and New York). Design: Retrospective, multicenter, IRB approved. Subjects: Eligible eyes had mild-moderate glaucoma and were treated with CP+TR with cataract surgery or as a standalone intervention. Methods: Main outcome measures were mean IOP, mean number of ocular hypotensive medications, mean change in number of medications, proportion of patients with a ≥20% reduction in IOP or with IOP ≤18 mmHg, and proportion of patients medication free. Safety outcomes were adverse events and secondary surgical interventions (SSI). Results: Eight surgeons at 7 centers contributed 72 patients stratified by pre-operative intraocular pressure (IOP); >18 mmHg (Grp1), ≤18 mmHg (Grp2). Mean follow-up of 2.1 years (min 1.4, max 3.5). 2-year IOP (SD) was 15.6 mmHg (-6.1 mmHg, -28% from baseline) on 1.4 medications (-0.9, -39%) for Grp1 with cataract surgery; 14.7 mmHg (-7.4 mmHg, -33% from baseline) on 1.6 medications (-0.7, -15%) for Grp1 standalone, 13.7 mmHg (-0.6 mmHg, -4.2%) on 1.2 medications (-0.8, -35%) for Grp2 with cataract surgery, 13.3 mmHg (-2.3 mmHg, -14.7%) on 1.2 medications (-1.0, -46%) for Grp2 standalone. The proportion of patients at 2 years with either a ≥20% IOP reduction or IOP between 6 and 18 mmHg and no increase in medication or SSI was 75% (54 of 72, 95% CI 69.9%, 80.1%). One-third of patients (24 of 72) were medication free whereas 9 of 72 were pre-surgical. No device-related adverse events during extended follow-up; 6 eyes (8.3%) required additional surgical or laser intervention for IOP control after 12 months. Conclusion: CP+TR provides effective IOP control that is sustained for 2 years or more.
RESUMO
PURPOSE: Provide outcomes up to 12 months postsurgically for sequential canaloplasty and trabeculotomy with the OMNI surgical system (Sight Sciences, Inc) in pseudophakic patients with mild to moderate open-angle glaucoma. DESIGN: Retrospective, multicenter, single-arm study conducted at 10 multi-subspecialty ophthalmology practices and surgery centers located in 7 states (Arkansas, California, Kansas, Louisiana, Missouri, New York, and Texas). PARTICIPANTS: Eligible patients were pseudophakic, with mild/moderate open-angle glaucoma, 12-month follow-up, and medicated intraocular pressure (IOP) ≤36 mmHg on ≤4 medications preoperatively. One eye per patient was enrolled. METHODS: Institutional Review Board approved. All available cases meeting eligibility criteria were enrolled. Analysis of secondary end points was stratified by baseline (BL) IOP (>18 mmHg in group 1 and ≤18 mmHg in group 2) recognizing that treatment goals differed depending on BL IOP. MAIN OUTCOME MEASURES: Primary success was defined as the proportion of patients with ≥20% reduction in IOP from BL or IOP between 6 and 18 mmHg (inclusive) and on the same or fewer medications without secondary surgical intervention (SSI). Other effectiveness end points included mean IOP and number of medications at 12 months. Safety end points were best-corrected visual acuity (BCVA), adverse events (AEs), and SSIs. RESULTS: Forty-eight patients were enrolled, 24 in each group. Primary success was met by 73%. Mean IOP was reduced in group 1 (21.8 to 15.6 mmHg, P < 0.0001) and remained controlled in group 2 (15.4 to 13.9 mmHg, P = 0.24). Medications went from 1.7 ± 1.3 to 1.2 ± 1.3 (P = 0.024) in group 1 and from 2.0 ± 1.3 to 1.3 ± 1.3 (P = 0.003) in group 2. Adverse events were typical for the patient population undergoing angle surgery. Those reasonably related to the procedure were mild inflammation (13%), IOP spikes (6%), hyphema, corneal edema, and BCVA loss (all 4%). Five patients (10%) required an SSI. CONCLUSIONS: The sequential combination of canaloplasty followed by trabeculotomy performed as stand-alone procedures using the OMNI system in pseudophakic patients with open-angle glaucoma provides effective IOP reduction or sustained IOP control and meaningful medication reduction for up to 12 months postoperatively.
Assuntos
Glaucoma de Ângulo Aberto , Trabeculectomia , Glaucoma de Ângulo Aberto/complicações , Humanos , Pressão Intraocular , Estudos Retrospectivos , Tonometria OcularRESUMO
PURPOSE: To provide safety and effectiveness outcomes 12 months postsurgically for sequential canaloplasty and trabeculotomy with the OMNI system combined with cataract surgery in mild-to-moderate open-angle glaucoma (OAG). SETTING: Eleven ophthalmology practices and surgery centers located in 8 U.S. states. DESIGN: Retrospective, multicenter, single arm. METHODS: Twelve surgeons contributed 81 patients meeting eligibility criteria: OAG, 12-month follow-up, and medicated intraocular pressure (IOP) 36 mm Hg or less on 4 or less medications preoperatively. Analysis was stratified by baseline IOP: more than 18 mm Hg (Group 1) and 18 mm Hg (Group 2) or less. Success was defined as proportion with 20% reduction or greater in IOP or IOP between 6 and 18 mm Hg (inclusive) and on the same or fewer medications without secondary surgical intervention (SSI). Other endpoints included mean IOP and medications at 12 months. Safety included corrected distance visual acuity and adverse events (AEs). RESULTS: Of the 81 patients included, primary success was met by 79% in Group 1 and 81% in Group 2. The mean IOP was reduced in Group 1 (21.9 to 15.1 mm Hg, P < .0001) and remained controlled in Group 2 (14.1 to 13.4 mm Hg, P = .3177). Medications went from 2.0 ± 1.3 to 1.1 ± 1.1 in Group 1 and from 1.6 ± 1.3 to 0.9 ± 1.2 in Group 2. AEs were typical for cataract or angle surgery: mild inflammation (11%), IOP spikes (5%), and hyphema (4%). Four patients (5%) required an SSI. CONCLUSIONS: The OMNI system provided effective IOP reduction, sustained IOP control, and meaningful medication reduction for up to 12 months postoperative.
Assuntos
Catarata , Glaucoma de Ângulo Aberto , Oftalmologia , Trabeculectomia , Catarata/complicações , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We describe the course and likely pathophysiology of impending anterior ischemic optic neuropathy (AION) and retinal vein occlusion in a 56-year-old man with polycythemia vera managed with interferon alpha for 2 years. Our patient presented with decreased vision, scintillating scotomata, and floaters. Fundus examination findings and results of a fluorescein angiogram led to the diagnosis of impending AION and retinal vein occlusion. Considering that both polycythemia vera and interferon have possible influences on vascular occlusion and optic disc edema, we stopped interferon treatment and immediately attempted to treat the polycythemia vera empirically with pentoxifylline and any interferon-associated inflammation with prednisone. Our patient experienced complete resolution of fundus abnormalities and return of normal vision within 3 weeks, which may be attributed to our successful treatment of both etiologies. Thus, further study is warranted to elucidate the treatment of both polycythemia vera and interferon-induced impending AION.