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Purpose: We discuss a peripheral combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) with a macula-involving TRD that was repaired by vitrectomy surgery. Methods: A case report is presented. Results: A 15-year-old white girl with no significant medical or ocular history presented to the retina clinic with a 1-month history of progressive loss of inferior visual field in the right eye. A large, elevated CHRRPE was found in the superior midperipheral retina. On involvement of the macula, urgent vitrectomy surgery with peeling of the cortical vitreous membrane to the margins of the hamartoma was performed. Eighteen months later, vision had returned to 20/16 and the retina, relieved of traction, continued to reattach with trace remaining cystic changes at the fovea on optical coherence tomography. Conclusions: Physicians should consider vitrectomy surgery with membrane peeling of the cortical vitreous for TRD due to CHRRPE.

Purpose To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD). Design Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials. Participants Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n = 32). Methods Changes in visual function and imaging/anatomic parameters were evaluated over time using a mixed model for repeated measurement accounting for key baseline characteristics. Main Outcome Measures Prespecified end points included change in GA area from baseline, best-corrected visual acuity (BCVA) score assessed by Early Treatment Diabetic Retinopathy Study (ETDRS), and visual acuity under low-luminance (LLVA). Results At 24 months, adjusted mean (standard error) change in GA lesion area from baseline was 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A), 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B). Progression of GA was greater in patients with baseline nonsubfoveal (vs. subfoveal) GA lesions and tended to increase as baseline low-luminance deficit increased (all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (standard error) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months were −13.88 (1.40) and −7.64 (1.20) in Proxima A, −9.49 (1.29) and −7.57 (1.26) in Proxima B fellow eye CNV cohort, and −11.48 (3.39) and −8.37 (3.02) in Proxima B fellow eye intermediate AMD cohort, respectively. Conclusions The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline.

Aims: Protocol T (NCT01627249) was a head-to-head study conducted by the Diabetic Retinopathy Clinical Research Network that compared intravitreal aflibercept, bevacizumab, and ranibizumab for the treatment of diabetic macular edema (DME). A cost-effectiveness analysis accompanying the 1-year data of Protocol T revealed that aflibercept was not cost-effective vs ranibizumab for all patients, but could have been cost-effective in certain patient sub-groups if the 1-year results were extrapolated out to 10 years. The present study evaluated the cost-effectiveness of US Food and Drug Administration-approved anti-vascular endothelial growth factor agents (ranibizumab, aflibercept) for treatment of DME using the 2-year data from Protocol T. Methods: Costs of aflibercept 2.0 mg or ranibizumab 0.3 mg, visual acuity (VA)-related medical costs, and quality-adjusted life-years (QALYs) were simulated for eight VA health states. Treatment, adverse event management, and VA-related healthcare resource costs (2016 US dollars) were based on Medicare reimbursement and published literature. VA-related health utilities were determined using a published algorithm. Patients were stratified by baseline VA: 20/40 or better; 20/50 or worse. Results: Total 2-year costs were higher, and QALYs similar, for aflibercept vs ranibizumab in the full cohort ($44,423 vs $34,529; 1.476 vs 1.466), 20/40 or better VA sub-group ($40,854 vs $31,897; 1.517 vs 1.519), and 20/50 or worse VA sub-group ($48,214 vs $37,246; 1.433 vs 1.412), respectively. Incremental cost-effectiveness ratios in the full cohort and 20/50 or worse VA sub-group were $986,159/QALY and $523,377/QALY, respectively. These decreased to $711,301 and $246,978 when analyses were extrapolated to 10 years. Limitations: Key potential limitations include the fact that VA was the only QALY parameter analyzed and the uncertainty surrounding the role of better- and worse-seeing eye VA in overall functional impairment. Conclusions: This analysis suggests that aflibercept is not cost-effective vs ranibizumab for patients with DME, regardless of baseline vision.

Background/objectives This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO). Subjects/methods Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses. Results Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P Conclusions Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO.

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.

The real-world performance of a home telemonitoring strategy (ForeseeHome AMD Monitoring System®, Notal Vision, Inc.,Manassas VA, USA) was evaluated and compared to the device arm of the AREDS2-HOME study among patients with intermediate AMD (iAMD) who converted to neovascular AMD (nAMD). All patients with confirmed conversion to nAMD who used the home monitoring system from 10/2009 through 9/2018 were identified by Notal Vision Diagnostic Clinic’s medical records. Selected outcome variables were evaluated, including visual acuity (VA) at baseline and at conversion, and change in visual acuity (VA) from baseline to time of conversion. In total, 8991 patients performed 3,200,999 tests at a frequency of 5.6 ± 3.2 times/week. The 306 eyes that converted from iAMD to nAMD over the study period (a 2.7% annual rate) were included in the analyses. There was a median (interquartile range) change of −3.0 (0.0–(−10.0)) letters among converted eyes, 81% [95% confidence interval (72–88%)] maintained a VA ≥ 20/40 at the time of conversion, while 69% of the conversion detections were triggered by system alerts. The real-world performance of an at-home testing strategy was similar to that reported for the device arm of the AREDS2-HOME study. The home telemonitoring system can markedly increase early detection of conversion to nAMD.

Purpose To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). Design Phase 3, open-label, randomized, visual acuity assessor–masked noninferiority and equivalence trial. Participants Patients with nAMD diagnosed within 9 months of screening previously treated with and responsive to anti–vascular endothelial growth factor therapy. Methods Patients were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/ml with fixed 24-week (Q24W) refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5-mg injections every 4 weeks (monthly ranibizumab). Main Outcome Measures Primary end point was change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter (letters) score from baseline averaged over weeks 36 and 40 (noninferiority margin,–4.5 letters; equivalence margin, ±4.5 letters). Results Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with the PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 letters (PDS Q24W arm) and 75.5 letters (monthly ranibizumab arm; Snellen equivalent, 20/32). Adjusted mean change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 letters (standard error [SE], 0.5 letters) in the PDS Q24W arm and +0.5 letters (SE, 0.6 letters) in the monthly ranibizumab arm (difference, –0.3 letters; 95% confidence interval, –1.7 to 1.1 letters). PDS Q24W was both noninferior and equivalent to monthly ranibizumab. Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4%) did not receive supplemental ranibizumab treatment before the first refill-exchange procedure, including 4 patients who discontinued treatment before the first refill-exchange procedure. Prespecified ocular adverse events of special interest were reported in 47 patients (19.0%) in the PDS Q24W arm and 10 patients (6.0%) in the monthly ranibizumab arm, which included, in the former arm, 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions. Most ocular adverse events in the PDS Q24W arm occurred within 1 month of implantation. Conclusions Archway met its primary objective and PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab, with 98.4% of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.

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.

BACKGROUND AND OBJECTIVE: Guidance on the use of corticosteroids in the treatment of diabetic macular edema (DME) is lacking. This study aimed to develop a clinically recommended treatment paradigm for DME with emphasis on the role of corticosteroids. PATIENTS AND METHODS: An expert panel of nine retinal specialists in the United States developed consensus recommendations for DME treatment through a modified Delphi process. RESULTS: The panelists typically use intravitreal injections of vascular endothelial growth factor (VEGF) antagonists as first-line treatment of DME and switch patients with an inadequate response to anti-VEGF therapy (failure of best-corrected visual acuity to improve to 20/40 or better because of edema after three to six monthly injections, or a less-than-50% reduction in excess macular thickness after three to four monthly injections) to intravitreal corticosteroid treatment. CONCLUSION: Intravitreal corticosteroids have a potentially useful role in the treatment of patients with DME who have an inadequate response to intravitreal anti-VEGF therapy. [ Ophthalmic Surg Lasers Imaging Retina. 2017;48:291–301.]

Oxygen levels in the eye are generally low and tightly regulated. Oxygen enters the eye largely by diffusion from retinal arterioles and through the cornea. In intact eyes, oxygen from the retinal arterioles diffuses into the vitreous body. There is a decreasing oxygen gradient from the retina to the lens, established by oxygen consumption by ascorbate in the vitreous fluid and lens metabolism. Age-related degeneration of the vitreous body or removal during vitrectomy exposes the posterior of the lens to increased oxygen, causing nuclear sclerotic cataracts. Lowering oxygen in the vitreous, as occurs in patients with ischemic diabetic retinopathy, protects against cataracts after vitrectomy. Vitrectomy and cataract surgery increase oxygen levels at the trabecular meshwork and with it the risk of open angle glaucoma. Two additional risk factors for glaucoma, African heritage and having a thinner cornea, are also associated with increased oxygen in the anterior chamber angle. Preservation of the vitreous body and the lens, two important oxygen consumers, would protect against nuclear sclerotic cataracts and open angle glaucoma. Delaying removal of the lens for as long as possible after vitrectomy would be an important step in delaying ocular hypertension and glaucoma progression.

The diabetic macular edema (DME) treatment paradigm has evolved as the understanding of the disease pathology has grown. Since 2012, four pharmacotherapies have been approved by the U.S. Food and Drug Administration for the treatment of DME. First-line treatment of DME with anti–vascular endothelial growth factor [VEGF] agents has become the gold standard; however, an appreciable percentage of patients do not respond to anti-VEGF therapies. In patients who inadequately respond to anti-VEGF therapies, the underlying disease pathology may be mediated by a multitude of growth factors and inflammatory cytokines. For these patients, corticosteroids are an attractive treatment option because they not only downregulate VEGF, but also an array of cytokines. The phase 3 MEAD and FAME trials demonstrated significant visual acuity improvements associated with dexamethasone and fluocinolone acetonide, respectively, in patients with DME; however, class-specific adverse events, including increased intraocular pressure and cataract development, must be considered before use. A panel of experts gathered during the 2015 annual meeting of the American Academy of Ophthalmology for a roundtable discussion focused on patient selection and adverse event management associated with the use of the 0.19 mg fluocinolone acetonide intravitreal implant. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:S5–S15.]

The lens is composed of a thin metabolically active outer layer, consisting of epithelial and superficial fibre cells. Lying within this outer shell are terminally differentiated, metabolically inactive fibre cells, which are divided into an outer cortex and central nucleus. Mature fibre cells contain a very high protein concentration, which is important for the transparency and refractive power of the lens. These proteins are protected from oxidation by reducing substances, like glutathione, and by the low-oxygen environment around the lens. Glutathione reaches the mature fibre cells by diffusing from the metabolically active cells at the lens surface. With age, the cytoplasm of the nucleus becomes stiffer, reducing the rate of diffusion and making nuclear proteins more susceptible to oxidation. Low pO2is maintained at the posterior surface of the lens by the physical and physiological properties of the vitreous body, the gel filling the space between the lens and the retina. Destruction or degeneration of the vitreous body increases exposure of the lens to oxygen from the retina. Oxygen reaches the lens nucleus, increasing protein oxidation and aggregation and leading to nuclear cataract. We suggest that maintaining low pO2around the lens should prevent the formation of nuclear cataracts.

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 To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). DESIGN Randomized clinical trial. PARTICIPANTS Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for

Purpose To evaluate the anatomic closure rate and visual outcome in patients undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling with and without indocyanine green (ICG) enhancement. Design Retrospective, noncomparative interventional case series. Participants One hundred ninety-three consecutive patients (204 eyes) seen at the Barnes Retina Institute with the clinical diagnosis of macular hole who underwent PPV between January 1998 and December 2000. Intervention A consecutive series of 97 patients undergoing PPV with or without unilateral epiretinal membrane removal without ILM peeling (group 1), 44 patients with PPV and ILM peeling without ICG (group 2), and 35 patients with ICG-assisted ILM peeling (group 3). Results Overall, 86.4% of the holes closed with one operation, with 75 of 97 (77.3%) eyes in group 1, 43 of 44 (97.7%) eyes in group 2, and 34 of 35 (97.1%) eyes in group 3 (χ 2 = 10.51, P = 0.007). Of the eyes that did not close, 18 patients in group 1 underwent repeat surgery, with 90 of 97 (92.8%) eyes ultimately achieving closure. Visual acuity after surgery was 20/50 or better in 55 of 97 (56.7%) patients, 31 of 44 (70.4%) patients, and 18 of 35 (51.4%) patients in groups 1, 2, and 3, respectively (χ 2 = 3.43, P = 0.18) and increased by 2 or more lines from their preoperative status in 63 of 97 (64.9%) patients, 34 of 44 (77.3%) patients, and 25 of 35 (71.4%) patients, respectively (χ 2 = 2.25, P = 0.32). Multivariate logistic regression demonstrated that use of ILM peeling during vitrectomy increases the chances of developing 20/50 vision or better (odds ratio [OR], 2.4; 95% confidence interval, 1.06–5.45; P = 0.04). No eyes received concurrent cataract extraction with macular hole surgery, but 75 of 166 (45.2%) required cataract extraction postoperatively. Complications included 20 retinal tears, 4 retinal detachments, and 34 patients with postoperative elevations in intraocular pressure (IOP; defined as IOP greater than 30 mmHg). Conclusions Although this study is limited by the shorter follow-up in patients undergoing ILM peeling with or without ICG relative to the control group, our experience indicates that the use of ILM peeling is associated with a statistically significant improvement in the rate of primary macular hole closure with a single operation.

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.

As recently as two decades ago, textbooks on vitreous taught students of ophthalmology that the vitreous gel had no real function in the adult eye other than to serve as a space-occupying, optically clear structure. In fact, one such textbook published in 1994 stated, “Apart from its role in oculogenesis, the vitreous has no well substantiated function so that an eye devoid of gel is not adversely affected” [1]. However, beginning in 2005 with published reports of oxygen tension measurements in the human vitreous gel before and after vitrectomy surgery [2] and culminating with reports in 2009 that the human vitreous gel consumes oxygen in an ascorbate-dependent manner [3], a new understanding of the vitreous gel and its role in vitreoretinal physiology and pathology has emerged.

Objective This study aimed to report the visual outcome of surgical removal of extensive peripapillary choroidal neovascularization (CNV) due to presumed ocular histoplasmosis syndrome (POHS). Design Retrospective review of the records of all patients seen at the Barnes Retina Institute who underwent surgical removal of extensive peripapillary CNV associated with POHS and who had at least 12 months of follow-up. Participants Seventeen consecutive eyes (in 14 patients) undergoing surgical removal of extensive peripapillary CNV associated with POHS were studied. Intervention Pars plana vitrectomy and surgical removal of CNV were performed. Main outcome measurements Best-corrected Snellen visual acuity, funduscopic examination, and intravenous fluorescein angiography were obtained before surgery and at regular intervals after surgery. Results In 14 of 17 eyes, the peripapillary CNV was subfoveal, and in 3 eyes, it was extrafoveal. All three eyes with extrafoveal CNV were not eligible for laser treatment according to Macular Photocoagulation Study guidelines because treatment would have spared less than 1.5 contiguous clock-hours of retina temporal to the optic disc. Follow-up ranged from 17 to 57 months, with a median of 32 months. In eyes with subfoveal CNV, best-corrected preoperative Snellen visual acuity ranged from 20/25 to counting fingers at 2 feet with a median of 20/200, and best-corrected final Snellen visual acuity ranged from 20/25 to 20/200 with a median of 20/40. In 7 (50%) of 14 eyes, a final Snellen acuity of 20/40 or better was achieved, and in all cases except 1, visual acuity improved or did not change with surgery. In the three eyes with extrafoveal CNV, best-corrected preoperative Snellen visual acuity ranged from 20/20 to 20/400 with a median of 20/200, and best-corrected final Snellen visual acuity was 20/20 in all cases. In addition, visual acuity improved with surgery. Conclusions The data from this small retrospective study suggest that surgical removal may provide visual benefit in selected cases of extensive peripapillary CNV due to POHS.

Purpose: The authors assess the stability of visual acuity outcomes after the surgical removal of subfoveal choroidal neovascularization in a large series of patients with presumed ocular histoplasmosis syndrome (PONS). Methods: A retrospective study of 117 consecutive patients undergoing vitrectomy between February 1990 and December 1994 was performed. All patients underwent the surgical removal of subfoveal choroidal neovascularization due to POHS and had at least 3 months of follow-up. Postoperative Snellen visual acuity was the primary study endpoint. Results: With a median follow-up of 13 months (range, 3–46 months), 35% of patients had postoperative visual acuity of 20140 or better, and 40% had improvement of three or more Snellen lines after surgery. In a subset of 54 eyes followed for at least 1 year, 91% showed stable or improved vision between the 3- and 12-month time points, and 85% showed stable or improved vision between 3 months and final visit. Conclusion: Follow-up of a large number of patients appears to confirm initially encouraging results and to suggest stability of beneficial effect after the surgical removal of subfoveal choroidal neovascularization in POHS.

Objective To compare the PO 2 distribution in different regions in the eyes of patients undergoing intraocular surgery. Methods Before initiation of intraocular cataract and/or glaucoma surgery, an optical oxygen sensor was introduced into the anterior chamber via a peripheral corneal paracentesis. The tip of the flexible fiberoptic probe was positioned by the surgeon for 3 measurements in all patients: (1) near the central corneal endothelium, (2) in the mid–anterior chamber, and (3) in the anterior chamber angle. In patients scheduled to undergo cataract extraction, PO 2 was also measured (4) at the anterior lens surface and (5) in the posterior chamber just behind the iris. Oxygen measurements at the 5 locations were compared using a 2-tailed unpaired t test and multivariate regression. Results The PO 2 value was significantly higher in African American patients at all 5 locations compared with Caucasian patients. Adjusting for age increased the significance of this association. Adjusting for race revealed that age was associated with increased PO 2 beneath the central cornea. Conclusions Racial differences in oxygen levels in the human eye reflect an important difference in oxidative metabolism in the cornea and lens and may reflect differences in systemic physiologic function. Increased oxygen or oxygen metabolites may increase oxidative stress, cell damage, intraocular pressure, and the risk of developing glaucoma. Oxygen use by the cornea decreases with age.

Objective To compare the incidence rates of myocardial infarction (MI) and cerebrovascular accident (CVA) in hospitalized patients with and without branch or central retinal vein occlusion (RVO). Methods In this retrospective cohort study, a US population-based health care claims database was used to identify patients with RVO and control patients, matched for age and sex. Events of MI, CVA, and covariates were identified for patients with and without RVO. Incidences of MI or CVA events prompting hospitalization and adjusted rate ratios (RRs) were calculated; RRs were adjusted for covariates consistent with risk factors for outcomes. Results Of 4500 patients with RVO and 13 500 controls, the event rates for MI were 0.87 per 100 person-years and 0.67 per 100 person-years, respectively. The adjusted RR for MI was 1.03 (95% confidence interval [CI], 0.75-1.42; P = .85 for RVO vs controls). Event rates for CVA were 1.16 and 0.52 per 100 person-years for RVO and controls, respectively. The adjusted RR for CVA was 1.72 (95% CI, 1.27-2.34; P = .001) for RVO vs controls. Conclusions This study provides quantitative data on the incidence of cardiovascular and cerebrovascular outcomes in patients with RVO in a large US population-based health care claims database. Event rates for MI were similar in patients with RVO and controls; however, the event rate for CVA in patients with RVO was almost 2-fold that observed in controls.

Objective To investigate the rate and mechanism of oxygen consumption by the vitreous. Methods Oxygen consumption was measured with a microrespirometer. Vitreous ascorbate was measured spectrophotometrically and by gas chromatography–mass spectrometry. Vitreous degeneration was related to the rate of oxygen consumption and ascorbate concentration in samples obtained during vitrectomy. Results Prolonged exposure to oxygen or treatment with ascorbate oxidase eliminated oxygen consumption by the vitreous. Adding ascorbate restored oxygen consumption. Oxygen consumption persisted after boiling or treating the vitreous with the chelating agents EDTA and deferoxamine. In patients undergoing retinal surgery, liquefaction of the vitreous and previous vitrectomy were associated with decreased ascorbate concentration and lower oxygen consumption. Conclusions Ascorbate in the vitreous decreases exposure of the lens to oxygen. The catalyst for this reaction is not known, although free iron may contribute. The gel state of the vitreous preserves ascorbate levels, thereby sustaining oxygen consumption. Vitrectomy or advanced vitreous degeneration may increase exposure of the lens to oxygen, promoting the progression of nuclear cataracts. Clinical Relevance Determining how the eye is protected from nuclear cataracts should suggest treatments to reduce their incidence.

BACKGROUND AND OBJECTIVE To compare the surgical outcome of scleral buckling (group 1) versus scleral buckling with pars plana vitrectomy (group 2) for the repair of macula-off rhegmatogenous retinal detachment without proliferative vitreoretinopathy. PATIENTS AND METHODS A retrospective chart review was performed. RESULTS Eighty-three patients were identified in group 1 and 63 patients in group 2. Presenting visual acuity was 4/200 in group 1 and 3/200 in group 2. Median duration of detachment prior to surgery was 5 days in group 1 and 6 days in group 2. There was no statistical difference in best-corrected (P = .59) or most recent (P = .75) visual acuity between groups. Median best-corrected visual acuity was 20/30 and median most recent visual acuity was 20/40 in both groups. Significantly more additional procedures were performed in group 1 than in group 2 (21.7% vs 7.9%, respectively; P = .024). The final reattachment rate was 96.4% in group 1 and 98.4% in group 2. Proliferative vitreoretinopathy developed in 15.7% of patients in group 1 and 4.8% in group 2 (P = .037). CONCLUSION Visual outcome of scleral buckling is similar to scleral buckling with pars plana vitrectomy for the treatment of macula-off rhegmatogenous retinal detachment in patients without proliferative vitreoretinopathy. Patients undergoing scleral buckling only are at an increased risk of developing proliferative vitreoretinopathy and requiring additional procedures. [Ophthalmic Surg Lasers Imaging 2009;40:539-547.] AUTHORS From the Department of Ophthalmology & Visual Sciences (PND, KJB, GKS, NMH, DPJ, BW, MAT, MGG), Washington University School of Medicine; and the Barnes Retina Institute (KJB, GKS, NMH, DPJ, MAT, MGG), St. Louis, Missouri. Accepted for publication December 16, 2008. Supported in part by the Heed Ophthalmic Fellowship Foundation. The authors have no financial or proprietary interest in the materials presented herein. Address correspondence to Kevin J. Blinder, MD, 1600 South Brentwood Boulevard, Suite 800, St. Louis, MO 63144. doi: 10.3928/15428877-20091030-02

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 report the long-term visual outcomes of surgical removal of extensive peripapillary choroidal neovascularization associated with presumed ocular histoplasmosis syndrome (POHS). Design Long-term retrospective review. Follow-up ranged from 14 to 139 months (mean, 68). Participants Forty consecutive eyes (in 35 patients) undergoing surgical removal of extensive peripapillary choroidal neovascularization associated with POHS at the Barnes Retina Institute between May 1992 and December 2003 were included in this review. Patient age ranged from 5 to 73 years (median, 34.5). All eyes were ineligible for laser treatment by Macular Photocoagulation Study criteria. Intervention Pars plana vitrectomy and surgical removal of choroidal neovascularization were performed. Main Outcome Measures Determination of Snellen best-corrected visual acuity (BCVA), funduscopic examination, and intravenous fluorescein angiography were done before surgery and at regular intervals after surgery. Results In the 23 eyes with subfoveal extension of peripapillary choroidal neovascularization, preoperative BCVA ranged from 20/25 to counting fingers (CF) at 2 feet (median, 20/200). Final postoperative BCVA ranged from 20/15 to CF at 2 feet (median, 20/50). Of 23 eyes, 18 achieved stable or improved BCVA from the preoperative to the final postoperative examination; only 5 eyes had ≥2 lines of decreased BCVA. Overall, 11 of 23 eyes achieved ≥20/40 BCVA at the final postoperative examination. In the 17 eyes in which choroidal neovascularization remained extrafoveal, preoperative BCVA ranged from 20/20 to 20/400 (median, 20/60). Final BCVA ranged from 20/20 to 20/200 (median, 20/20). Of 17 eyes, 15 achieved stable or improved BCVA from preoperative to final postoperative examination; only 2 eyes had ≥2 lines of decreased BCVA. Overall, 14 of 17 eyes achieved ≥20/40 BCVA at the final postoperative examination. Conclusions The data from this small retrospective study suggest that surgical removal may provide visual benefit in selected cases of extensive peripapillary choroidal neovascularization associated with POHS. Surgical removal of extensive peripapillary choroidal neovascularization does appear preferable to photoablation. Given the likelihood of multiple treatments with photodynamic therapy or anti–vascular endothelial growth factor therapies, surgical removal provides a potentially efficacious treatment with low recurrence rates and good visual results.

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.

Pseudophakic cystoid macular edema is now an infrequent complication of cataract surgery. However, since cataract surgery continues to be one of the most commonly performed surgical procedures, the prevalence of pseudophakic cystoid macular edema is high. In addition, although pseudophakic cystoid macular edema has been a well-defined entity since the 1950s and 1960s, little progress has been made in understanding its pathogenesis or in deriving an effective treatment of the condition. While acute pseudophakic cystoid macular edema may resolve spontaneously, chronic visually significant pseudophakic cystoid macular edema remains difficult to treat. Nonsteroidal anti-inflammatory agents and corticosteroids in various forms can be used, but each type of treatment lacks satisfactory success. Eyes with abnormal vitreous or refractory to medical therapy can be improved with vitrectomy surgery. It must be concluded, however, that there is a real need for significant advances in both the understanding and treatment of pseudophakic cystoid macular edema.

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.

To evaluate the use of ocular photodynamic therapy (OPT) with verteporfin in patients with choroidal neovascularization (CNV) from ocular histoplasmosis syndrome (OHS) and to compare these results with those for a natural history group.A retrospective chart review was performed to identify cases of CNV secondary to OHS treated with OPT. Complete data were available for 38 of 41 eligible eyes. Data regarding the following variables were abstracted from the patient charts: demographic characteristics, previous surgery, angiographic features, number and timing of treatments with OPT, follow-up time, and visual acuity. The visual acuity results of eyes receiving photodynamic therapy were compared with those for a natural history cohort.On average, OHS patients who received treatment developed 0.88 line of visual improvement. Visual acuity improved or stayed the same in 69% (22 of 32) of eyes, improved byor = 2 lines in 44% (14 of 32), and improved byor = 4 lines in 22% (7 of 32). Patients who received OPT were 2.07 times more likely to have improved or constant vision than were those in the natural history group as described in one retrospective series (odds ratio = 2.07; 95% confidence interval, 0.78-5.56; P = 0.162). Thirty-eight percent (12 of 32) of eyes had undergone submacular surgery for CNV before any OPT.Ocular photodynamic therapy with verteporfin may be beneficial in patients with CNV secondary to OHS, even in the setting of previous submacular surgery.

Szilárd Kiss,1 Ying Liu,2 Joseph Brown,3 Nancy M Holekamp,4,5 Arghavan Almony,6 Joanna Campbell,2 Jonathan W Kowalski2 1Weill Cornell Medical College, New York, NY; 2Allergan, Inc., Irvine, CA; 3IMS Health, Woodland Hills, CA; 4Pepose Vision Institute, Chesterfield, MO; 5Washington University School of Medicine, St Louis, MO; 6Carolina Eye Associates, Southern Pines, NC, USA Purpose: To examine the utilization of bevacizumab and ranibizumab and disease monitoring in patients with branch or central retinal vein occlusion (BRVO/CRVO) or diabetic macular edema (DME) in clinical practice.Patients and methods: This retrospective claims analysis included newly diagnosed patients with one or more bevacizumab or ranibizumab injections. Bevacizumab or ranibizumab utilization was assessed by year of first injection:2008–2010cohorts (12-month follow-up), January to June2011cohort (6-month follow-up). The main outcome measures were mean annual numbers of injections, ophthalmologist visits and optical coherence tomography examinations, and proportion of patients with additional laser or intravitreal triamcinolone (IVTA) use.Results: A total of885BRVO,611CRVO, and2,733DME patients treated with bevacizumab were included, with too few ranibizumab-treated patients for meaningful analysis. Across the2008,2009, and2010cohorts, mean annual numbers of bevacizumab injections increased, but remained low (BRVO2.5,3.1,3.3; CRVO3.1,3.1,3.5; and DME2.2,2.5,3.6, respectively); mean ophthalmologist visits ranged between4.4and6.5, and mean optical coherence tomography examinations ranged between3.1and3.9across all conditions. A total of42.0% of BRVO,16.5% of CRVO, and57.7% of DME patients received additional laser or IVTA therapy. The number of bevacizumab injections was positively associated with laser use in BRVO (3.3versus2.9, P

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.

Several lines of evidence suggest that increased oxidative stress or the accumulation of oxidative damage contributes to the pathogenesis of glaucoma.1–7 Antioxidant protective mechanisms are decreased, and enzymes induced by oxidative stress are increased in the aqueous humor of glaucoma patients, compared with those undergoing cataract surgery.3,8 Oxidative damage to DNA increases in the trabecular meshwork cells of glaucoma patients, and these cells are more susceptible to oxidative DNA damage than are other cells in the anterior segment.9 In one study, the lymphocytes of glaucoma patients had pathogenic mutations in their mitochondrial DNA that were not present in control subjects.10 These alterations are consistent with oxidative damage. The mitochondria of glaucoma patients also had significantly lower oxidative activity than in control subjects.10 Despite the abundant evidence linking glaucoma's pathogenesis to oxidative damage, the source of the oxidative stress in these patients is not known. It is also not clear whether the increased oxidative damage in glaucoma patients is the result of increased exposure to oxidants, decreased antioxidative protection, or a combination of these factors. Ocular surgery can increase the risk of developing glaucoma. Elevated intraocular pressure and glaucoma have long been associated with corneal transplantation (penetrating keratoplasty) or the implantation of an artificial cornea.11–19 Recently, two studies reported that vitrectomy is also associated with increased risk of elevated intraocular pressure and glaucoma. In both studies, the presence of the natural lens delayed the onset of glaucoma.20,21 In most older patients who undergo vitrectomy, nuclear sclerotic cataracts develop within 2 years.22–26 Nuclear cataract is associated with increased oxidative damage to the lens, and vitrectomy leads to increased exposure of the lens to oxygen.23,27,28 These observations led Chang20 to propose that, after vitrectomy, metabolites of oxygen, like hydrogen peroxide, may damage the tissues of the outflow pathway, contributing to the increased risk of glaucoma. Since the presence of the natural lens reduces the risk of glaucoma, he proposed that the lens protects the anterior segment from oxygen or oxygen metabolites. The present study was designed to test Chang's hypothesis that oxygen is relatively low in the anterior segment of the non–surgically altered eye and that it increases after vitrectomy and cataract surgery. The distribution of oxygen in the anterior segment of the eye was measured in a reference group of patients who were undergoing surgery for glaucoma or cataract. Oxygen distribution in these patients was compared with that in patients who had had vitrectomy, cataract surgery, or both procedures. The results of these measurements supported the predictions of the Chang hypothesis, which suggest that increased exposure to oxygen or its metabolites causes open-angle glaucoma. These studies also revealed an unexpected physiologic mechanism that regulates the distribution of oxygen in the anterior chamber angle of the human eye.

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.

PURPOSE: To describe and compare methods used to monitor development and progression of presumed vision-limiting lens opacity in study eyes of Submacular Surgery Trials (SST) patients. DESIGN: Prospective study of patients enrolled in a set of randomized clinical trials. PARTICIPANTS: Patients enrolled in the SST who were phakic in the study eye at the time of enrollment (n = 690). In a subset of 114 patients, lens photographs were obtained at baseline and 2 years after enrollment. METHODS: Data collection at baseline and annual follow-up examinations included ocular history, ophthalmologic examination including the SST ophthalmologist's assessment of presence or absence of vision-limiting opacity, fundus photography, and lens photography (13 of 27 clinics only). All photographs were assessed by masked graders centrally using the Lens Opacities Classification System III (LOCS III). kappa statistics were calculated to compare LOCS III cataract classifications with fundus photograph quality and with the ophthalmologist's assessment of lens opacity, with the LOCS III classification considered the gold standard. MAIN OUTCOME MEASURE: Incidence of cataract in study eyes. RESULTS: Baseline lens photographs were available and graded for 312 (45%) of 690 patients with phakic study eyes; 2-year lens photographs were available for 156 (23%) of 690 initially phakic eyes. Both baseline and 2-year lens photographs were available for 114 eyes that remained phakic. Submacular surgery was associated with significant progression of nuclear color and nuclear opalescence characteristics within 2 years of enrollment. The reliability of fundus photograph quality versus cataract classification using a 4.5 LOCS III score threshold for cataract was poor to good at each time point and for all groups (kappa, 0-0.51), but sensitivity of the photograph quality score as a surrogate was low, and both positive and negative predictive values were low. Agreement between the ophthalmologists' assessments of lens opacity and the 4.5 LOCS III score threshold for cataract was good (kappa, 0.42-0.78). CONCLUSIONS: In the SST, clinical identification of severe cataract (LOCS III scores of 4.5 or worse for nuclear opacity or nuclear color) by the examining ophthalmologist was valid based on comparison with LOCS III scores and may be an adequate method to use in similar trials.

Objective To investigate intraocular penetration of moxifloxacin hydrochloride after oral administration. Methods Prospective study of 15 patients scheduled for vitrectomy between September and November 2004 at the Barnes Retina Institute, St Louis, Mo. Aqueous, vitreous, and serum samples were analyzed from 15 patients after oral administration of 2 tablets containing 400 mg of moxifloxacin. Assays were performed using high-performance liquid chromatography. Results The mean ± SD moxifloxacin concentrations in plasma (n = 15), vitreous (n = 13), and aqueous (n = 13) samples were 3.56 ± 1.31 μg/mL, 1.34 ± 0.66 μg/mL, and 1.58 ± 0.80 μg/mL, respectively. Mean ± SD sampling times after oral administration of the second moxifloxacin tablet for plasma, vitreous, and aqueous were 2.94 ± 0.81 hours, 3.77 ± 0.92 hours, and 3.71 ± 0.89 hours, respectively. The percentages of plasma moxifloxacin concentration in the vitreous and aqueous were 37.6% and 44.3%, respectively. Minimal inhibitory concentrations against 90% levels were exceeded against a wide spectrum of gram-positive and gram-negative pathogens in the vitreous and aqueous. Conclusions Moxifloxacin has a spectrum of coverage that encompasses the most common organisms in endophthalmitis. The pharmacokinetic findings of this investigation reveal that orally administered moxifloxacin achieves therapeutic levels in the noninflamed eye. Because of their broad spectrum of coverage, low minimal inhibitory concentration against 90% levels, good tolerability, and excellent oral bioavailability, fourth-generation fluoroquinolones may represent a major advance for managing posterior segment infections.

Objective To investigate the penetration of 0.5% moxifloxacin hydrochloride into the aqueous and vitreous after topical administration in humans. Methods A prospective, nonrandomized study of 20 patients scheduled for vitrectomy surgery between September 1 and December 31, 2003. Aqueous and vitreous samples were obtained and analyzed after topical administration of 0.5% moxifloxacin hydrochloride, every 2 hours (q2h) or every 6 hours (q6h), for 3 days before surgery. Assays were performed using high-performance liquid chromatography. Results Mean ± SD moxifloxacin concentrations in the q2h group for the aqueous (n = 9) and vitreous (n = 10) were 2.28 ± 1.23 and 0.11 ± 0.05 μg/mL, respectively. Mean ± SD moxifloxacin concentrations in the q6h group for the aqueous (n = 10) and vitreous (n = 9) were 0.88 ± 0.88 and 0.06 ± 0.06 μg/mL, respectively. The minimum inhibitory concentration for 90% of isolates (MIC 90 ) was far exceeded in the aqueous for a wide spectrum of key pathogens, whereas it was not exceeded in the vitreous for several organisms. However, the minimum inhibitory concentration for 50% of the isolates was exceeded in the q2h vitreous group for Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Bacillus cereus, and other gram-negative pathogens. Conclusions The Endophthalmitis Vitrectomy Study revealed that 94.2% of isolates from postoperative endophthalmitis are gram-positive pathogens. Moxifloxacin has a spectrum of coverage that appropriately encompasses the most common organisms in endophthalmitis. The pharmacokinetic findings of this investigation show that relatively high aqueous levels can be achieved after topical administration. Further studies will help define the precise role of 0.5% moxifloxacin ophthalmic solution in the treatment of or prophylaxis against intraocular infections.

PURPOSE. Vitrectomy is associated with the rapid progression of nuclear cataracts. This study was conducted to test the hypothesis that age-related liquefaction of the vitreous gel may also be associated with lens opacification. METHODS. Lenses from eye bank eyes were graded for nuclear, cortical, and posterior subcapsular opacities, and the amount of liquid vitreous was measured. RESULTS. Nuclear sclerosis (NS) grade, percent liquefaction, and age all correlated highly (P 0.0001). After adjustment was made for age, the correlation between NS and percent liquefaction was 0.37 (P 0.0001), and the correlation between age and NS after adjustment for liquefaction was 0.57 (P 0.0001). After the eyes were stratified into age groups, the correlation between NS and percent liquefaction was found to be highest in eyes from donors aged 51 to 70. Cortical and posterior subcapsular opacities increased with age, but scores for these cataract types did not significantly correlate with vitreous liquefaction. CONCLUSIONS. Loss of vitreous gel during aging increases the risk of nuclear cataracts. Preservation or replacement of the vitreous gel may protect patients from nuclear cataract. (Invest Ophthalmol Vis Sci. 2004;45:77‐ 85) DOI:10.1167/iovs.030820

Objective To report a series of patients manifesting ulnar neuropathy as an extraocular complication following macular hole surgery and facedown positioning. Methods Retrospective chart review of 7 patients identified by the operating surgeon as developing ulnar neuropathy during the immediate postoperative period after undergoing vitrectomy surgery with fluid-gas exchange for macular hole followed by at least 1 week of strict facedown positioning. Results All 7 patients developed symptoms of ulnar neuropathy, including paresthesias, dysesthesias, pain, weakness, and muscle atrophy. Signs included abnormal electromyogram, prolonged nerve conduction velocities, and impaired neurologic clinical test results in patients examined. Symptoms did not resolve with cessation of facedown positioning, and with follow-up ranging from 3 to 24 months all patients had persistent symptoms. All patients had positioned themselves with their arms continuously flexed. Three of 7 patients had placed pressure directly on their bent elbows. Conclusions Ulnar neuropathy is an extraocular complication of macular hole surgery that can be attributed to arm position during postoperative facedown positioning. Surgeons performing macular hole surgery should caution their patients to minimize the amount of time spent with their elbows in a flexed position. Particular effort should be made to minimize pressure on the bent elbow.

The report by Freeman et al 1 on "Vitrectomy for the Treatment of Full-Thickness Stage 3 or 4 Macular Holes: Results of a Multicentered Randomized Clinical Trial" in the January 1997 issue of theArchivesdescribed a notable incidence of adverse events. One complication, the postoperative appearance of retinal pigment epithelial (RPE) changes causing window defects in the macula in 11 (17%) of 64 patients, is particularly important and intriguing. It is important because a trend toward worsening visual acuity was associated with RPE changes. Of the 20 eyes in the surgery group that had a postoperative decrease in visual acuity, 11 had RPE changes. It is intriguing because this complication is only rarely reported in other large series of macular hole surgery. In fact, an incidence of only 1% was reported in a retrospective study of 98 patients. 2 Perhaps the surgical protocol adhered to by the study's investigators

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 [