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PURPOSE : To investigate the relationship between retinal fluid and vision in ranibizumab-treated patients with neovascular age-related macular degeneration (nAMD). DESIGN Clinical cohort study using post hoc analysis of clinical trial data. METHODS : Setting: HARBOR (NCT00891735): phase III, randomized, controlled trial. Population: 917 patients aged ≥50 years with subfoveal nAMD associated with subretinal (SRF) and/or intraretinal fluid (IRF) at baseline, screening, or week 1. Intervention: Intravitreal ranibizumab 0.5 or 2.0 mg (all treatment arms pooled). Outcomes: Mean best-corrected visual acuity (BCVA) and BCVA change from baseline at months (M)12/24 evaluated by presence/absence of SRF and/or IRF. RESULTS : Baseline BCVA was higher with residual versus resolved SRF at M12 (mean [95% confidence interval (CI)], 58.8 letters [57.2 to 60.4] vs 53.5 [52.4 to 54.5]) and M24 (59.3 letters [57.8 to 60.8] vs 53.5 [52.5 to 54.5]). Mean BCVA change (adjusted for baseline) to M12 was greater with residual versus resolved SRF (mean difference [95% CI], +2.4 letters [+0.1 to +4.7]), but lower with residual versus resolved IRF (−3.5 letters [−5.8 to −1.2]). Eyes with residual SRF (no IRF) exhibited the largest mean BCVA gains (M12, +14.1 letters; M24, +13.2), followed by resolved SRF/IRF (M12, +10.6 letters; M24, +10.0), residual SRF/IRF (M12, +7.2 letters; M24, +8.5), and residual IRF only (M12, +5.5 letters; M24, +3.6). CONCLUSIONS : Vision outcomes (adjusted for baseline BCVA) through M24 were better in ranibizumab-treated eyes with residual versus resolved SRF, and worse with residual versus resolved IRF. Presence of residual retinal fluid requires a more complex and nuanced assessment and interpretation in the context of nAMD management.

Purpose To determine monitoring and treatment patterns, and vision outcomes in real-world patients initiating anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME). Design Retrospective interventional cohort study. Methods: SETTING Electronic medical record analysis of Geisinger Health System data. STUDY POPULATION 110 patients (121 study eyes) initiating intravitreal ranibizumab or bevacizumab for DME during January 2007‒May 2012, with baseline corrected visual acuity of 20/40‒20/320, and ≥1 ophthalmologist visits during follow‐up. MAIN OUTCOME MEASURES Intravitreal injections per study eye during the first 12 months; corrected visual acuity, change in corrected visual acuity from baseline, proportions of eyes with ≥10 or ≥15 approxEarly Treatment Diabetic Retinopathy Study letter gain/loss at 12 months; number of ophthalmologist visits. Results Over 12 months, mean number of ophthalmologist visits was 9.2; mean number of intravitreal injections was 3.1 (range, 1–12), with most eyes (68.6%) receiving ≤3 injections. At 12 months, mean corrected visual acuity change was +4.7 letters (mean 56.9 letters at baseline); proportions of eyes gaining ≥10 or ≥15 letters were 31.4% and 24.0%, respectively; proportions of eyes losing ≥10 or ≥15 letters were 10.8% and 8.3%, respectively. Eyes receiving adjunctive laser during the first 6 months (n = 33) showed similar change in corrected visual acuity to non–laser-treated eyes (n = 88) (+3.1 vs +5.3 letters at 12 months). Conclusions DME patients receiving anti-VEGF therapy in clinical practice undergo less frequent monitoring and intravitreal injections, and achieve inferior vision outcomes to patients in landmark clinical trials.

Purpose To describe the expanding role of telemedicine in healthcare, the key criteria required for a successful device and program implementation, and the current and future role of home monitoring in ophthalmology. Design Expert perspective. Methods Analysis with real-world interpretation of home monitoring technologies, including current adoption barriers and expanded future demands based on demographic and market forces. Results Remote patient monitoring represents a paradigm shift in the way physicians care for patients. Success depends on meeting several criteria, among which are a recognized value proposition to the physician, robust device performance validation, ease of use for the patient, reliability of connectivity, safe and secure data transmission, and economic feasibility. Ophthalmic diseases, such as age-related macular degeneration, glaucoma, and diabetic retinopathy, are ideal candidates for home monitoring practice integration. Established home monitoring technology is already facilitating early detection and improved visual outcomes for patients with age-related macular degeneration. Future innovation currently underway or on the horizon will continue to evolve and expand the footprint of telemedicine within ophthalmology. Conclusion Home monitoring has the potential to enhance the patient-physician relationship and to positively impact visual acuity outcomes in ophthalmic diseases. Advances in technology, demographic shifts, market changes, and patient demand for personalized medicine will require physicians to embrace technology in new and diverse ways, perhaps facilitating widespread adoption of home monitoring technology platforms.

To report intraocular oxygen tension in eyes of diabetic and nondiabetic patients.A prospective, interventional consecutive case series.Oxygen was measured with an optical oxygen sensor in patients who were undergoing vitrectomy. Before turning on the infusion fluid, intraocular oxygen tension was measured in two locations: adjacent to the lens and in the mid vitreous cavity.Fifty eyes from 50 patients were included in the study. Twenty-one eyes were from diabetic patients and 29 eyes were from nondiabetic patients. The mean oxygen tension adjacent to the lens was significantly lower in diabetic than in nondiabetic patients (8.4 +/- 0.7 mm Hg vs 10.7 +/- 0.8 mm Hg; P.05). Similarly, the mean oxygen tension in the center of the vitreous cavity was lower in diabetic than in nondiabetic patients (5.7 +/- 0.7 mm Hg vs 8.5 +/- 0.6 mm Hg; P.001). In subgroup analyses, previous panretinal photocoagulation or cataract surgery did not affect oxygen levels significantly in the vitreous of diabetic or nondiabetic patients.Eyes from diabetic patients have significantly lower intraocular oxygen tension than in eyes from nondiabetic patients. Because oxidative damage to the lens nucleus and increased intraocular oxygen tension have been associated with nuclear sclerotic cataract, these findings may help explain recent reports of an apparent protective effect of diabetes mellitus against nuclear sclerotic cataract.

Purpose To report the feasibility and safety profile of 2-mg and 6-mg fluocinolone acetonide implants after long-term follow-up in eyes with choroidal neovascularization (CNV). Design Prospective, noncomparative, interventional case series of patients with non-age-related subfoveal choroidal neovascularization enrolled in a compassionate use protocol. Methods Sustained drug delivery devices containing either 2 mg (eight eyes) or 6 mg (six eyes) of fluocinolone acetonide were implanted through the pars plana into the vitreous cavity of 14 patients with predominantly classic, subfoveal CNV. The main outcome measures were complications related to the device. Secondary outcome measures were involution of established CNV, inhibition of recurrent CNV, and visual acuity. Results Patients had a diagnosis of ocular histoplasmosis (seven), myopic degeneration (four), angioid streaks (two), and punctate inner choroidopathy (one). Patients were followed for an average of 33 months (range, 16 to 40 months). All 14 eyes developed elevated intraocular pressure and cataract. Four eyes developed nonischemic central retinal vein occlusion. Complications required implant removal in 8 eyes. Ten of 14 eyes demonstrated involution of CNV or inhibition of recurrent CNV. Ten eyes had stable or improved visual acuity. Median initial visual acuity was 20/64. Median final visual acuity was 20/40. Conclusions Long-term follow-up demonstrates a significant complication rate with the sustained release of high-dose intraocular corticosteroids. The complications are treatable, and eyes can retain good vision. This therapeutic approach warrants further study to identify if lower doses of corticosteroids may reduce the complication rate yet still be effective in treating ocular disease.

PURPOSE: Pigment epithelium-derived growth factor (PEDF) is a potent inhibitor of angiogenesis that is found in the normal eye. The purpose of this study is to report decreased levels of PEDF in the vitreous of eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). DESIGN: Prospective case-control study. METHODS: In a prospective case-control study, undiluted vitreous was collected from nine eyes of nine patients with CNV due to AMD and from an age-matched control group of 12 eyes of 12 patients with retinal disorders not involving neovascularization. Vitreous PEDF and vascular endothelial growth factor (VEGF) concentrations were determined by Western blot analyses and enzyme-linked immunosorbent assay (ELISA), respectively. Angiogenic activities of the vitreous samples were assessed in vitro using an endothelial cell chemotaxis assay. RESULTS: In vitreous samples from nine eyes with CNV due to AMD the mean ± SD PEDF level was 2.8 ng/μl ± 1.3 ng/μl. In vitreous samples from 12 age-matched control eyes the mean ± SD PEDF level was 16.4 ng/μl ± 7.1 ng/μl. The difference between the two groups was statistically significant ( P = .00003). No significant difference in vitreous VEGF concentration was seen between CNV/AMD samples and control samples ( P = .23). All CNV/AMD vitreous samples induced endothelial cell migration in vitro. No sample from age-matched non-age-related macular degeneration controls could induce endothelial cell migration, and 11 of 12 were able to block VEGF-induced migration in vitro. This inhibitory activity required active PEDF. CONCLUSION: The vitreous of patients with CNV due to AMD contained lower levels of PEDF and lacked the antiangiogenic activity of vitreous from age-matched controls. This suggests that loss of PEDF creates a permissive environment for CNV patients with AMD.

Purpose To define the role of intravitreal bevacizumab in individuals with choroidal neovascularization (CNV) resulting from Ocular Histoplasmosis syndrome (OHS). Design Retrospective chart review of a surgical therapy. Methods We reviewed the course of 28 eyes of 28 patients who underwent intravitreal injection of bevacizumab for treatment of CNV secondary to OHS. Outcome was measured by pretreatment and posttreatment visual acuity (VA). Results The average pretreatment logarithm of the minimum angle of resolution (logMAR) VA was 0.65 (Snellen equivalent of 20/88). Mean follow-up was 22.43 weeks with an average of 1.8 intravitreal injections. Average final logMAR VA was 0.43 (Snellen equivalent of 20/54). Twenty eyes (71%) experienced an increase in central VA, whereas four eyes (14%) were unchanged and four eyes (14%) experienced a decrease in vision. Conclusions Intravitreal bevacizumab may improve or stabilize VA in a significant majority of patients with neovascular complications of OHS (24 eyes [85.7%] in our study population).

Purpose To evaluate the safety of intravitreal Macugen (OSI/Eyetech, New York, New York, USA) injections among patients receiving warfarin anticoagulation. Design Retrospective chart review. Methods A search was conducted for patients treated with intravitreal Macugen for choroidal neovascularization resulting from age-related macular degeneration (AMD). Inclusion criteria included patients receiving warfarin anticoagulation in whom therapy was maintained. Results The review identified 31 patients (32 eyes) who underwent 102 intravitreal Macugen injections while receiving warfarin anticoagulation. The mean and median number of Macugen injections per patient was three. No intraoperative or immediate postoperative hemorrhagic complications were noted. One patient experienced an acute submacular hemorrhage 35 days after the third Macugen injection. There were no other hemorrhagic events among the remaining patients. Conclusions The retrospective chart review of patients treated with intravitreal Macugen for choroidal neovascularization resulting from AMD while receiving warfarin therapy suggests that patients may undergo intravitreal injections safely without cessation of anticoagulation therapy.

To report vitreous oxygen tension before, immediately after, and at longer times after vitrectomy.A prospective, interventional consecutive case series.Oxygen was measured using an optical oxygen sensor in patients undergoing vitrectomy. Intraoperatively, oxygen measurements were taken before and after vitrectomy in two intraocular locations: adjacent to the lens and in the mid-vitreous.Sixty-nine eyes underwent oxygen tension measurements at the time of vitrectomy. In baseline eyes, oxygen tension in the vitreous was low, measuring 8.7 +/- 0.6 mm Hg adjacent to the lens and 7.1 +/- 0.5 mm Hg in the mid-vitreous. The difference between the two locations was statistically significant (P.003), indicating that vitreous gel maintains an intraocular oxygen gradient. Immediately after vitrectomy, oxygen tension in the fluid-filled eye was higher, measuring 69.6 +/-4.8 mm Hg adjacent to the lens and 75.6 +/- 4.1 mm Hg in the mid-vitreous. There was no statistically significant oxygen gradient between the two locations. The difference in oxygen tension pre- and postvitrectomy is highly statistically significant (P.0001 lens, P.0001 mid-vitreous). In eyes with a history of vitrectomy and previous removal of the vitreous gel, the intraocular oxygen tension was significantly higher than in eyes with a formed vitreous gel undergoing a first vitrectomy (P.02 lens, P.003 mid-vitreous).Vitrectomy surgery significantly increases intraocular oxygen tension during and for prolonged periods after surgery. This exposes the crystalline lens to abnormally high oxygen and may lead to nuclear cataract formation.

Purpose To determine the safety of pars plana vitrectomy in eyes containing a treated posterior uveal melanoma. Design Interventional case series. Methods Retrospective case series of patients with posterior uveal melanoma who underwent pars plana vitrectomy. Complications, vitreous cytology, local tumor control, and metastasis were assessed. Results Nine patients met study criteria. Tumors were treated with 125 I plaque radiotherapy (seven patients) or transpupillary thermotherapy (two patients). Vitrectomy was performed for vitreous hemorrhage (five patients), macular pucker (two patients), macular hole (one patient), and rhegmatogenous retinal detachment (one patient). Vitrectomy was performed at a mean of 24.7 months (range, 7–47 months) after melanoma treatment. Dispersion of tumor cells at vitrectomy was not observed in any patients. Melanoma cells were detected in the vitreous aspirate in one of seven cases examined cytologically. This patient had intratumoral and vitreous hemorrhage before plaque radiotherapy, underwent combined vitrectomy/cataract extraction, and developed intraocular tumor dissemination 56 months after vitrectomy. No other patients developed intraocular tumor dissemination. At mean follow-up of 24 months (range, 3–63 months) after vitrectomy, none of the nine patients developed systemic metastasis. Conclusions Pars plana vitrectomy rarely may lead to intraocular tumor dissemination, although the risk of this complication is probably low if the tumor has been treated and has responded to therapy before vitrectomy. Vitrectomy should be approached with caution if a vitreous hemorrhage is present, especially if the hemorrhage occurred before tumor treatment, as this may seed tumor cells into the vitreous cavity.

Purpose To study the possible association between clear corneal incision with or without placement of a suture during cataract extraction and postoperative endophthalmitis. Design Retrospective, comparative, case-controlled study. Methods Thirty-eight patients treated for culture-positive, acute postcataract surgery endophthalmitis, and 371 randomly selected control patients who underwent uncomplicated cataract surgery in the referring community were studied. Incision type and use of suture during cataract surgery of endophthalmitis patients were compared with the controls. The data were analyzed using logistic regression methods. Results Of the 38 patients with endophthalmitis, 17 patients (45%) had clear corneal incisions and 21 patients (55%) had a scleral tunnel incision. In 371 controls, 76 patients (20%) had clear corneal incisions and 295 patients (80%) had scleral tunnel incisions. Clear corneal incision was associated with a threefold greater risk of endophthalmitis than was scleral tunnel incision (Odds Ratio, 3.36, 95% Confidence Interval=1.67 to 6.78). The type of incision was significant (χ 2 = 11.53, P = .0007); a clear corneal incision was more frequently associated with endophthalmitis. A subgroup analysis revealed that the presence or absence of a suture was not significant (χ 2 = 1.31, P = .2524). Conclusions In this retrospective, case-controlled study, clear corneal incisions were found to be a statistically significant risk factor for acute postcataract surgery endophthalmitis when compared with scleral tunnel incisions.

Pigment epithelium-derived growth factor (PEDF) is a potent inhibitor of angiogenesis that is found in the normal eye. The purpose of this study is to report decreased levels of PEDF in the vitreous of eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).Prospective case-control study.In a prospective case-control study, undiluted vitreous was collected from nine eyes of nine patients with CNV due to AMD and from an age-matched control group of 12 eyes of 12 patients with retinal disorders not involving neovascularization. Vitreous PEDF and vascular endothelial growth factor (VEGF) concentrations were determined by Western blot analyses and enzyme-linked immunosorbent assay (ELISA), respectively. Angiogenic activities of the vitreous samples were assessed in vitro using an endothelial cell chemotaxis assay.In vitreous samples from nine eyes with CNV due to AMD the mean +/- SD PEDF level was 2.8 ng/microl +/- 1.3 ng/microl. In vitreous samples from 12 age-matched control eyes the mean +/- SD PEDF level was 16.4 ng/microl +/- 7.1 ng/microl. The difference between the two groups was statistically significant (P =.00003). No significant difference in vitreous VEGF concentration was seen between CNV/AMD samples and control samples (P =.23). All CNV/AMD vitreous samples induced endothelial cell migration in vitro. No sample from age-matched non-age-related macular degeneration controls could induce endothelial cell migration, and 11 of 12 were able to block VEGF-induced migration in vitro. This inhibitory activity required active PEDF.The vitreous of patients with CNV due to AMD contained lower levels of PEDF and lacked the antiangiogenic activity of vitreous from age-matched controls. This suggests that loss of PEDF creates a permissive environment for CNV patients with AMD.

Purpose To examine bevacizumab and ranibizumab utilization and disease monitoring patterns in patients with neovascular age-related macular degeneration (neovascular AMD) in clinical practice. Design Retrospective medical claims analysis. Methods Patients receiving ≥1 ranibizumab or bevacizumab injection during the 12 months after initial neovascular AMD diagnosis were included. Annual bevacizumab and/or ranibizumab injection utilization was assessed by year of first injection cohorts: 2006 and 2007 (received either agent because of billing code overlap), 2008, 2009, and January-June 2010 (received each agent). Outcome measures were time to first injection relative to neovascular AMD diagnosis and mean numbers of intravitreal injections, ophthalmologist visits, and optical coherence tomography (OCT) and fluorescein angiography (FA) examinations in 12 months. Results In the 2006 and 2007 cohorts (n = 8767), mean annual numbers of bevacizumab or ranibizumab injections were 4.7 and 5.0, respectively. Over 92% of patients in all cohorts received first treatment within 3 months of neovascular AMD diagnosis. In the 2008-2010 cohorts (n = 10 259), mean annual number of injections remained low (bevacizumab: 4.6, 5.1, and 5.5; ranibizumab: 6.1, 6.6, and 6.9), as did mean numbers of ophthalmologist visits (bevacizumab only) and OCT examinations (both agents), but there was no such trend in FA examinations. Conclusions Compared with treatment paradigms validated by clinical trials published at the time, in clinical practice, patients with neovascular AMD received fewer bevacizumab or ranibizumab injections and less-frequent monitoring from 2006 to mid-2011. Factors contributing to this lower injection frequency and visual outcomes associated with reduced utilization need to be researched.

To determine whether diabetes mellitus is protective for nuclear sclerotic cataract at baseline and 6 and 12 months after vitrectomy surgery.Prospective, interventional cohort study.Phakic diabetic and nondiabetic patients undergoing vitrectomy surgery for a variety of retinal conditions underwent Scheimpflug lens photography in the operated and fellow eye at baseline and at 6 and 12 months after vitrectomy surgery.Of 52 eyes included in the analysis, 23 eyes were from diabetic patients, 14 of which had surgery for ischemic retinopathy. At baseline, eyes with ischemic diabetic retinopathy had less nuclear sclerotic cataract than nonischemic diabetic and nondiabetic eyes. This was true for eyes undergoing vitrectomy surgery (P = .0001) and for fellow eyes (P = .003). Nuclear sclerotic cataract developed after vitrectomy surgery in nonischemic diabetic eyes and nondiabetic eyes at the same rate. Diabetic eyes with ischemic retinopathy showed no significant progression of nuclear opacification, and therefore had significantly less postvitrectomy nuclear cataract at 6 months (P1 × 10(-6)) and at 12 months (P.001) than nondiabetic or nonischemic diabetic eyes. Normalizing to baseline opacity and adjusting for age and other comorbidities did not alter this result.Ischemic diabetic retinopathy, not just systemic diabetes mellitus, protected against nuclear sclerotic cataract at baseline and after vitrectomy surgery. These findings are consistent with the hypothesis that increased exposure to oxygen is responsible for nuclear cataract formation.

Purpose To reexamine the role of the vitreous gel in ocular health and disease based on recent information in the ophthalmic literature. Design Perspective. Methods Review, analysis, and discussion of the implications of selected pertinent literature. Results A new understanding of the vitreous gel is emerging, placing it central to many disease processes affecting the eye, including diabetic retinopathy, retinal vein occlusion, age-related macular degeneration, nuclear sclerotic cataract, and primary open-angle glaucoma. The vitreous gel recently has been found to have the important function of oxygen regulation and distribution within the eye. As the gel undergoes age-related liquefaction or surgical removal this function is impaired. The resultant elevated intraocular oxygen tension likely proves beneficial for vascular endothelial growth factor–mediated retinal diseases. However, it may lead to oxidative stress within the eye and may contribute to disease states such as nuclear cataract and primary open-angle glaucoma. Conclusions An intact gel vitreous is central to a healthy human eye. We now understand that age-related liquefaction of the vitreous gel accompanies several age-related ocular diseases. The field of ophthalmology would benefit from future research to understand age-related vitreous liquefaction and to identify its cause.

PURPOSE: To report persistent open retinotomy after submacular surgery in patients with presumed ocular histoplasmosis. METHODS: Retrospective review. Five eyes of 5 patients with submacular choroidal neovascularization associated with presumed ocular histoplasmosis had pars plana vitrectomy, detachment of the posterior hyaloid, and surgical removal of the neovascular complex using the small retinotomy technique. All eyes were followed postoperatively for a mean of 47 months (range, 36 to 73 months). RESULTS: In all 5 patients, the open retinotomy persisted after submacular surgery. No complications were associated with the presence of an open retinotomy. CONCLUSION: Persistence of the retinotomy site may occur after submacular surgery. With follow-up of at least 36 months, no significant complication is associated with an open retinotomy site.

PurposeTo determine whether early visual acuity response to ranibizumab in diabetic macular edema is associated with long-term outcome.DesignPost hoc analysis of randomized controlled trial data.MethodsPooled data from the ranibizumab plus prompt and deferred laser treatment arms of the Diabetic Retinopathy Clinical Research Network's Protocol I study were used to explore the relationship between early (week 12) and late (weeks 52–156) visual acuity response (mean change from baseline in best-corrected visual acuity [CFB BCVA]; categorized improvement [