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Purpose: To determine the relationship between plasma concentrations of the C-C chemokines CCL2, CCL3, CCL4, and CCL5 and intermediate age-related macular degeneration (iAMD) patients compared with control inidividuals to further define the inflammatory pathways associated with age-related macular degeneration.Methods: The concentrations of CCL2, CCL3, CCL4, and CCL5 were measured using multiplex assays in plasma collected from 210 patients with iAMD and 102 control individuals with no macular degeneration as defined by multi-modal imaging. Non-inflammatory data included in the analysis were: age, sex, family history of AMD, history of smoking, body mass index, presence of reticular pseudo-drusen and cardiovascular disease. Median concentrations as well as a cutoff value for each chemokine were compared between the two groups.Results: The median concentrations of CCL2 and CCL4 did not differ between control and iAMD groups, however, CCL2 was elevated in iAMD when a cutoff comparison was used (p < 0.05). Median CCL3 and CCL5 concentrations were significantly decreased in the macular degeneration group compared with controls (p < 0.001) as well as when a cutoff value comparison was used. CCL3 and CCL5 were negatively correlated in cases and positively correlated in controls.Conclusions: Plasma CCL3 and CCL5 concentrations were significantly decreased and CCL2 concentrations were increased in patients with iAMD compared with controls, suggesting a role for C-C chemokines in the systemic inflammatory processes associated with disease development.

Purpose To determine the effect of metformin on early Nd:YAG laser treatment for posterior capsule opacification (PCO) and to explore a molecular mechanism to explain a possible protective effect of metformin against PCO. Methods We conducted: 1) a retrospective cohort study of patient eyes undergoing phacoemulsification at our institution; and 2) laboratory investigation of the effect of metformin on the behavior of lens epithelial cells in the context of an animal model for PCO. Population-averaged Cox proportional hazards modeling was used to estimate risk for time to Nd:YAG. For laboratory studies, expression of markers for epithelial-to-mesenchymal transition (EMT) implicated in PCO pathogenesis was measured in tissue culture and following extracapsular lens extraction in a mouse model. Results The rate of Nd:YAG laser capsulotomy was 13.1% among the 9798 eyes. Both metformin use and diabetes were protective factors for Nd:YAG laser capsulotomy in univariate analysis. However, in multivariable analysis with nondiabetics as the reference group, only metformin use among diabetics was significantly protective of Nd:YAG (hazard ratio: 0.68, 95% CI: 0.54-0.85, P = 0.0008), while eyes of patients with diabetes without metformin use did not significantly differ (P = 0.5026). Treatment of lens epithelial cells with metformin reduced the level of the EMT markers ⍺-SMA and pERK induced by TGF-β2. Similarly, metformin treatment reduced ⍺-SMA expression in lens epithelial cells following extracapsular lens extraction in a mouse model. Conclusions The protective effect of metformin against early Nd:YAG may relate to its ability to downregulate EMT in residual lens epithelial cells that otherwise trend toward myofibroblast development and PCO.

Purpose: The purpose of this study was to determine if the use of menopausal hormone therapy (HT) is related to the development of neovascular (NV) age-related macular degeneration (AMD), geographic atrophy (GA) and/or early/intermediate AMD.Methods: A case-control study was conducted from patients prospectively recruited from July 2014 to June 2019. Cases were females with AMD recruited into a registry and controls were females with age-related cataract and no AMD. Age-related macular degeneration was categorized into NV-AMD, GA, and early/intermediate. Hormone therapy (historic and current) was self-reported by the patient and categorized as ever/never use. Adjusted odds ratios (ORs) from multinomial logistic regressions are presented for each AMD group.Results: Female AMD case patients (n = 409) and controls (n = 132) were included in the analytic database. Almost half (45.5%) of the female AMD patients had NV-AMD, 14.9% had GA, and 39.6% had early/intermediate AMD. Among all study participants, 285 (52.7%) reported historic and/or current use of HT. Controls were significantly more likely to have any HT use (71.2%), compared to 43.0% (p ≤ 0.001) of NV-AMD patients, 47.5% (p = .002) of GA patients, and 50.6% (p ≤ 0.001) of early/intermediate AMD patients. Adjusted for potential confounders of age and Caucasian race, cases were significantly more likely to have lower HT use compared to controls: NV-AMD, OR = 0.31 (95%CI: 0.18-0.54), GA, OR = 0.40 (95%CI: 0.20-0.80), and early/intermediate AMD, OR = 0.36 (95%CI: 0.22-0.61).Conclusion: Our case-control study found that the use of HT was associated with a lower odds of all AMD stages studied: NV-AMD, GA and early/intermediate.

Purpose To study new and existing risk factors related to age-related macular degeneration (AMD) phenotypes in a Colorado cohort. Methods Age-related macular degeneration was categorized into early, intermediate, or advanced forms. Controls (n = 180) were patients with cataract and no AMD. Demographic and clinical data were gathered by patient interview and verified by chart review. Image data were reviewed by vitreoretinal specialists. Statistical analysis included univariable and multivariate logistic regression analysis (P Results Among the 456 patients with AMD, 157 (34.4%), 80 (17.6%), and 219 (48.0%) had the early/intermediate, geographic atrophy, and neovascular forms of the disease, respectively. Adjusted for age, African-American race was associated with a reduced risk of early/intermediate (adjusted odds ratio [AOR] = 0.08, confidence interval [CI] = 0.01-0.67) and neovascular AMD (AOR = 0.15, CI = 0.03-0.72). A family history of AMD was a risk factor for early/intermediate (AOR = 4.08, CI = 2.30-7.25), geographic atrophy (AOR = 8.62, CI = 3.77-19.7), and neovascular AMD (AOR = 3.76, CI = 2.16-6.56). A history of asthma was related to the early/intermediate form of AMD (AOR = 2.34, CI = 1.22-4.46). Conclusion Studying AMD in specific populations may reveal novel risk factors such as our finding of a relationship between asthma history and AMD.

PURPOSE: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. The role of systemic inflammation in AMD remains unclear specifically in patients with intermediate AMD (iAMD). We sought to determine whether systemic inflammation was associated with future iAMD progression. METHODS: Combinations of 27 circulating inflammatory markers including complement factors, cytokines, chemokines, and high-sensitivity C-reactive protein (hsCRP) were evaluated in iAMD patients recruited into a Colorado AMD registry. Systemic inflammatory markers were combined using principal component analysis. Risk factors for AMD progression were evaluated using Cox regression models. RESULTS: This study included 99 subjects with iAMD, 21 of which progressed to advanced AMD. Two principal components (PCs) were identified that contributed to risk for progression to advanced AMD, after adjusting for age and bilateral reticular pseudodrusen. The strongest associated PC was explained largely by the pro-inflammatory cytokine TNFα and the anti-inflammatory IL1ra antagonist of IL1. The additional PC was largely explained by IL6, IL8, C3 and factor D in the positive direction and CRP, MCP1, factor B and factor I in the negative direction. CONCLUSION: When evaluated through multivariate analyses, combinations of biomarkers distinguished patients who did and did not progress to future advanced AMD. Increased risk could result from different combinations of analyte levels indicating a complex relationship rather than a simple increase in a few markers. This suggests that studying systemic inflammation in iAMD can provide insights into early pathologic events and potentially identify patients at highest risk for the development of severe AMD.

Lay abstract This study investigated the use of quantum dots (QDs) to treat very advanced retinitis pigmentosa (RP), a disease characterized by progressive loss of peripheral and then central vision. QDs are sometimes called ‘artificial atoms’. If they are injected into the eye, they settle in the retina, the light-sensing layer of cells that is damaged by RP. When light enters the eye, it is absorbed by the QDs in the retina, and the light energy is converted to electrical energy. Electrical stimulation has been shown to benefit degenerating retina, as occurs in RP, and hence QDs may have the potential to improve or preserve vision in people with RP. This preliminary study recruited 20 people with very severe RP and injected QDs into their eyes. We aimed to see whether the QDs were safe. No adverse reactions were attributed to the QDs, and the average vision of treated eyes improved, whereas the participants’ untreated fellow eyes showed no real change in vision. Although encouraging, these results are only preliminary, and a larger study is planned to explore these findings.

Purpose To determine, using an aptamer-based technology in patients with intermediate age-related macular degeneration (AMD), (1) if there is a difference in plasma levels of 4979 proteins in patients with and without reticular pseudodrusen (RPD), and (2) if plasma levels of proteins are related to time to conversion to advanced AMD. Methods Patients with intermediate AMD and RPD were identified from an AMD registry. Relative concentrations of each protein were log (base 2) transformed and compared between patients with and without RPD using linear regression. A Cox proportional hazards survival model was fit to each aptamer to quantify associations with time to conversion. A pathway analysis was conducted in converters versus non-converters using the Reactome database. Results Of the 109 intermediate AMD patients, 39 had bilateral RPD (36%). Two proteins, TCL1A and CNDP1, were lower in patients in the intermediate AMD group with RPD. Twenty-one patients converted to advanced AMD with a median time to conversion of 25.2 months (range, 2.3-48.5 months) and median follow-up time in non-converters of 26.4 months (range, 0.03-49.7 months). Several proteins (lysozyme C, TFF3, RNAS6, and SAP3) distinguished patients who converted from those who did not convert to advanced AMD. The top conversion pathways included tumor necrosis factors bind their physiological receptors, digestion and absorption, signaling by activin, and signaling by TGF-β family members. Conclusions We identified a protein signature related to RPD, as well as to conversion to advanced AMD. The pathway analysis suggests that dysfunction of critical systemic pathways may have links to conversion to advanced AMD. Translational relevance Biomarkers identified in plasma likely reflect systemic alterations in protein expression in patients with intermediate AMD.

Purpose C-reactive protein (CRP) and decreased choroidal thickness (CT) are risk factors for progression to advanced age-related macular degeneration (AMD). We examined the association between systemic levels of CRP and CT in patients with intermediate AMD (iAMD). Methods Patients with iAMD in the Colorado AMD Registry were included. Baseline serum samples and multimodal imaging including spectral domain–optical coherence tomography (SD-OCT), fundus photography, and autofluorescence were obtained. Medical and social histories were surveyed. CT was obtained by manual segmentation of OCT images. High-sensitivity CRP levels were quantified in serum samples. Univariate and multivariable linear regression models accounting for the intrasubject correlation of two eyes were fit using log-transformed CT as the outcome. Results The study included 213 eyes from 107 patients with a mean age of 76.8 years (SD, 6.8). Median CT was 200.5 µm (range, 86.5–447.0). Median CRP was 1.43 mg/L (range, 0.13–17.10). Higher CRP was associated with decreased CT in the univariate model (P = 0.01). Older age and presence of reticular pseudodrusen (RPD) were associated with decreased CT (P < 0.01), whereas gender, body mass index, and smoking were not associated with CT. Higher CRP remained significantly associated with decreased CT after adjustment for age and RPD (P = 0.01). Conclusions Increased CRP may damage the choroid, leading to choroidal thinning and increased risk of progression to advanced AMD. Alternatively, CRP may be a marker for inflammatory events that mediate ocular disease. The results of this study further strengthen the association between inflammation and AMD. Translational Relevance Increased CRP is associated with choroidal thinning, a clinical risk factor for AMD.

Background/purpose To report a case of simultaneous endophthalmitis and anterior segment ischemia (ASI) that occurred in a patient after strabismus surgery. This is the first known case of both complications occurring at the same time. Methods Case report. Results A 60-year-old woman presented with eye pain and loss of vision 6 days after uncomplicated strabismus surgery for thyroid eye disease. On examination, she had corneal edema, anterior segment fibrin, an atonic iris, and no view to the posterior segment. On fluorescein angiography of the anterior segment, a large portion of the iris was nonperfused. Posterior segment ultrasound showed dense vitritis and a choroidal abscess. Intraoperative cultures grew methicillin-resistant Staphylococcus aureus. Conclusions Endophthalmitis and anterior segment ischemia are both exceedingly rare complications of strabismus surgery. It is possible that each one occurred independently, but more likely one process potentiated the other. One possible mechanism is inflammation-induced thrombosis.

To assess driving status, habitual visual acuity (VA) in the better-seeing eye, and self-reported driving difficulty among patients diagnosed with age-related macular degeneration (AMD).Cross-sectional cohort study of 553 AMD patients' habitual VA, self-reported driving status, and driving difficulty at time of interview.Patients diagnosed with AMD and recruited into the University of Colorado registry.Measurement of habitual VA by median logarithm of the minimum angle of resolution (logMAR) and Snellen equivalent, as well as 3 categories: 20/40 or better, 20/50 or 20/60, and worse than 20/60. Driving difficulty was self-reported on the 25-item National Eye Institute Visual Function Questionnaire.Self-reported driving status and driving difficulty.A total of 394 patients (71.2%) reported currently driving at time of study interview. Drivers were significantly younger than nondrivers (mean age, 76.7 years vs. 83.9 years; P0.0001) and were more likely to be men (42.6% vs. 25.8%; P = 0.0002). Median habitual VA in the better-seeing eye was better among drivers: 0.097 logMAR (Snellen equivalent, 20/25) versus 0.301 logMAR (Snellen equivalent, 20/40) for nondrivers (P0.0001). Among drivers, habitual VA was 20/40 or better for 87.6% of patients, 20/50 to 20/60 for 9.6% of participants, and worse than 20/60 for 2.8% of participants. Driving patients with habitual VA in the better-seeing eye of 20/40 or better reported less difficulty driving compared with patients with 20/50 or worse VA.In our study, most patients with AMD who were currently driving had at least 20/40 VA in the better-seeing eye. However, 12.4% of patients had VA of 20/50 or worse and reported more difficulties with driving. As the aging population continues to grow with increasing lifespan, the number of patients with AMD will increase, and discussion of driving and VA will become more clinically and legally pertinent.

We introduce a new method to observe the morphologic features of the vitreous with spectral-domain optical coherence tomography (SD-OCT) by evaluating and describing the posterior vitreous structure of various selected cases using enhanced high-density (HD) line mode.This is a descriptive case series of SD-OCT images with enhanced HD line at Denver Health Medical Center, University of Colorado School of Medicine, in 2014. The medical records with ocular images for these patients were analyzed.Enhanced HD line in vitreoretinal mode with SD-OCT offered wide images with well-visible vitreoretinal interface. The posterior precortical vitreous pocket (PPVP), often mistaken as a posterior vitreous detachment on standard retina-based cross line mode, was easily identified. Vitreomacular adhesion and traction, absence or presence of connecting channels between PPVP and Cloquet's canal, liquefied vitreous lacuna, and emulsified silicone oil droplet-layer could be observed.SD-OCT using enhanced HD line in vitreoretinal mode enables clear visualization of the posterior vitreous structure and often reclassifies patients previously thought to have a posterior vitreous detachment.

BACKGROUND AND OBJECTIVE: To evaluate the role of nonmydriatic ultrawide-field (UWF) color retinal imaging as a screening tool in the follow-up of asymptomatic patients after cataract extraction surgeries. PATIENTS AND METHODS: A retrospective, observational case series. A review of electronic medical records identified patients after cataract extraction followed with UWF retinal imaging (Optos 200Tx; Optos, Dunfermline, Scotland). Images were graded and reviewed by a retina specialist. Outcome measures included image quality, the detection of peripheral lesions, and association with perioperative risk factors. RESULTS: Seventy-six eyes of 58 consecutive patients were enrolled. A good visualization of the peripheral retina was accomplished in more than 90% of patients. Peripheral lesions were identified in 40 eyes (52.6%) with no surgery-related retinal breaks and/or detachments. Additional pathologies were found in 35 eyes (46.1%). CONCLUSION: Nonmydriatic UWF color retinal imaging was found to be a useful screening tool in the follow-up of asymptomatic patients after cataract extraction in this series. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:50–55.]

To purpose if this study was to determine whether the horizontal rectus muscle tendons (HRMTs) can be observed using anterior segment optical coherence tomography (AS-OCT) and to determine the repeatability of its measurements. Also, this study aimed to observe and measure the different external ocular structures at the level of the horizontal rectus muscle (HRM) insertion. This was a retrospective, observational, descriptive and comparative study. Images were obtained utilizing the RTVue 100 CAM system. Eyes were analyzed at the three and nine o’clock position. Scans were performed for three different locations: the limbus, the ciliary body and the equator. All scans were analyzed by two graders, separately and blinded. Measurements were performed for: HRMT length; HRM thickness; conjunctival epithelium thickness; conjunctiva and Tenon’s capsule thickness; scleral thickness; and external ocular thickness. Results were obtained from twenty eyes of ten volunteers. The conjunctival epithelium thickness was 52.33 μm, the total conjunctiva/Tenon’s capsule thickness was 313.54 μm, the medial rectus (MR) thickness was 136.63 μm and the lateral rectus (LR) thickness was 181.65 μm. The MR tendon length was 1,426.88 μm, the LR tendon length was 1,433.65 μm, the scleral thickness was 489.91 μm and the total external ocular structure thickness was 785.17 μm. Intra-observer reproducibility (intraclass correlation coefficient [ICC]) for tendon length was 0.993 for grader #1, 0.989 for grader #2; the muscle thickness ICC was 0.990 for grader #1 and 0.981 for grader #2. The inter-observer reproducibility ICC for tendon length was 0.557; the ICC for muscle thickness was 0.834. It is possible to visualize and measure HRMTs using AS-OCT. Measurements of the HRM, as well as the surrounding external ocular tissues, can be achieved.

Purpose: To describe the long-term outcome of a patient with multifocal choroiditis, who underwent surgical removal of a type 2 choroidal neovascular membrane employing 23 G pars plana vitrectomy. Observations: A 50-year-old man was treated with 3 monthly intravitreal bevacizumab injections, but despite treatment, visual acuity continued to worsen from 20/40 to 20/100, and bleeding was not receding. A minimal invasive pars plana vitrectomy was performed for surgical removal of the neovascular complex without any complicating incident. Subsequent visual acuity was 20/25 for more than eleven years. Conclusions and Importance: Surgical removal of choroidal neovascular membranes employing minimal invasive surgery in addition to anti-VEGF therapy, and OCT evaluation can be a viable approach for selected cases of juxtafoveal type 2 CNV. Keywords: Choroidal neovascular membrane, Spectral-domain optical coherence tomography, Pars plana vitrectomy, Anti-VEGF therapy

Purpose To explore top-ranked plasma proteins related to neovascular age-related macular degeneration (AMD) and geographic atrophy (GA), and explore pathways related to neovascular AMD and GA. Methods We conducted a pilot study of patients with neovascular AMD (n = 10), GA (n = 10), and age-matched cataract controls (n = 10) who were recruited into an AMD registry. We measured 4001 proteins in ethylenediaminetetraacetic acid plasma samples using an aptamer-based proteomic technology. Relative concentrations of each of 4001 proteins were log (base 2) transformed and compared between cases of neovascular AMD and GA versus controls using linear regression. Pathway analysis was conducted using pathways downloaded from Reactome. Results In this pilot study, higher levels of vinculin and lower levels of CD177 were found in patients with neovascular AMD compared with controls. Neuregulin-4 was higher and soluble intercellular adhesion molecule-1 was lower in patients with GA compared with controls. For neovascular AMD, cargo trafficking to the periciliary membrane, fibroblast growth factor receptor 3b ligand binding and activation, and vascular endothelial growth factor-related pathways were in the top ranked pathways. The top-ranked pathways for GA included several related to ErbB4 signaling. Conclusions We found different proteins and different pathways associated with neovascular AMD and GA. Vinculin and some of the top-ranked pathways have been previously associated with AMD, whereas others have not been described. Translational relevance Biomarkers identified in plasma likely reflect systemic alterations in protein expression and may improve our understanding of the mechanisms leading to AMD.

Purpose: To determine the effect of intravitreal anakinra on choroidal neovascularization (CNV) in an animal model.Methods: Laser photocoagulation used to rupture Bruch’s membrane; animals then assigned to groups based on varying frequency of intravitreal anakinra injections. At day 30, digital angiography was used to measure the CNV area. Result: Intravitreal anakinra dose-dependently inhibited CNV growth. Injections given one time resulted in a 26% reduction in CNV; in the once weekly group, a 41% reduction was seen; in the twice-weekly group, a 62% reduction was seen (all p < .001). Conclusion: Suppressing IL-1 function may provide another therapeutic avenue in exudative AMD.

Purpose To describe the ophthalmic findings in patients with Danon disease, an X-linked condition causing cardiomyopathy in males and females. Design Retrospective case series. Participants Patients with genetically proven Danon disease. Methods Retrospective chart review of complete eye examinations including electroretinogram, visual fields, and fluorescein angiography. Results Five females (4 affected) and 2 affected males were examined. The 4 affected females demonstrated a peripheral pigmentary retinopathy. Lens changes, myopia, abnormal electroretinogram and visual fields were also found. The males demonstrated a near-complete loss of pigment in the retinal pigment epithelium. Conclusion We report the first description of a characteristic retinopathy in patients with Danon disease and the first extracardiac manifestations in affected females. Retinopathy potentially could be used to identify asymptomatic carriers.

Paracentral occlusive retinopathy is an uncommon manifestation of sickle cell disease. If macular ischemia is not reversed, permanent vision loss can result. The authors report the successful use of exchange transfusion to treat unilateral paracentral occlusive retinopathy secondary to sickle cell disease in a 23-year-old man with hemoglobin SS disease. Initial presentation demonstrated arteriolar occlusion, perivenous hemorrhages, vessel tortuosity, and areas of retinal ischemia. Visual acuity was count fingers, and the patient noted a paracentral scotoma. Following transfusion, there was restoration of arteriolar flow as documented with fluorescein angiogram, and visual acuity returned to 20/20. [ Ophthalmic Surg Lasers Imaging Retina . 2013;44:505–507.]

Purpose: To report a case-series of central retinal vein occlusion that occurred in young, healthy patients after periods of intense exercise. Design: Retrospective chart review. Methods: Seven eyes of six patients with central retinal vein occlusion after exercise were assessed. Visual acuity, intraocular pressure, and physical examination evidence of neovascularization were recorded on presentation and follow-up visits. Some patients had optical coherence tomography done on both initial and final visits and some had only one optical coherence tomography performed. One eye had no light perception at the time of diagnosis and was excluded from statistical calculations involving visual acuity. Results: Patients were all males without any significant medical history. All patients had complete blood work, including hypercoagulable workup. Results were normal and no underlying cause was ever identified. Mean age was 37.6 years. The mean duration of symptoms before examination was 12.4 weeks. The average time that patients were observed was 170 days. On presentation, the average logarithm of the minimum angle of resolution value and standard deviation of visual acuity were 0.113 ± 0.198. The decimal acuity at this time was 0.83 ± 1.98 lines with the Snellen equivalent of 20/28.33 ± 1.92 lines. The average logarithm of the minimum angle of resolution value and standard deviation of final visual acuity were 0.081 ± 0.179. The decimal acuity was 0.9 ± 1.79 lines and the Snellen equivalent was 20/25.6 ± 1.79 lines. Mean intraocular pressure was 16.9 with standard deviation of 6.025. Range of intraocular pressure was 7 to 30 mmHg. Central retinal thickness as measured by optical coherence tomography ranged from 200 to 700 μm. No complication developed as a result of central retinal vein occlusion during the follow-up period. Conclusion: Central retinal vein occlusion may occur in young, healthy patients after intense exercise. The exact precipitating event is unknown, but may be a combination of factors, including transiently increased intravascular and intraocular pressure, dehydration, and increased blood viscosity.

Purpose: To propose a model that measures the effect of intravitreal bevacizumab (IVB) on relatively healthy retina. The purpose is to analyze the remote effect of a branch retinal vein occlusion in the healthy retina, to determine the response it may have to IVB, and to determine if IVB has an atrophic effect on the healthy retina. Methods: Retrospective, longitudinal comparative analysis of patients with branch retinal vein occlusion treated with IVB. Eyes were divided into experimental (branch retinal vein occlusion eye) and control (contralateral eye) groups. Each eye was analyzed for thickness and area. Thickness measurements were performed for total retinal thickness, inner retina thickness, and outer retina thickness. Area was measured for photoreceptors, choroid, and total retina. Results: Eighteen eyes of 9 patients. For thickness analysis, 1,050 scans were studied, and 126 measurements were performed on 42 scans for area analysis. No difference was observed for thickness, except for inner retina thickness. No difference was observed for area. No difference was observed when analyzing a cumulative exposure to IVB. Conclusion: There is no evidence to suggest an atrophic effect caused by IVB when analyzing thickness or area in this experiment. This model could be used to analyze the long-term safety of IVB in larger studies.

Age-related macular degeneration is a chronic disease leading to progressive central vision loss. It is the leading cause of irreversible blindness in the United States, most commonly affecting white Caucasians aged more than 55 years. Typical symptoms include decreased central vision, central scotoma, and metamorphopsia. Patients with acute loss of vision should be promptly referred to an ophthalmologist. New antiangiogenic therapies have significantly improved visual prognosis in these patients.

Cyclodialysis clefts occur when the attachment of the ciliary body to the scleral spur is disrupted. The mechanism is usually traumatic or iatrogenic after phacoemulsification or other intraocular manipulation. Treatment becomes necessary when hypotony occurs, with maculopathy being the most visually significant sequela. A patient who failed conventional treatment for hypotony and eventually benefited from a novel surgery to correct his cyclodialysis cleft is described. [Ophthalmic Surg Lasers Imaging 2006;37:151153.]

A 74-year-old man presented with a 6-month history of a pigmented conjunctival lesion on his left eye. The lesion was initially suspicious for conjunctival melanoma. The patient admitted to a remote history of trauma from a airgun pellet over 60 years ago. Anterior examination revealed a 6 x 6 mm pigmented left conjunctival lesion and B-scan of the lesion was suggestive of a retained orbital foreign body. The lesion was removed through a transcaruncular medial orbitomy and pathology showed a retained orbital foreign body. A newly pigmented conjunctival lesion although initially concerning for melanoma represented a retained orbital body that surfaced many years after the initial orbital trauma.

The objective of this study was to compare the reduction in size of experimentally induced choroidal neovascularization (CNV) in rat eyes treated with bevacizumab, poly(ethylene-glycol) (PEG)-bevacizumab conjugate (b-PEG), and poly(lactic-co-glycolic acid) (PLGA)-encapsulated bevacizumab (b-PLGA).Forty-eight eyes from 24 rats were divided into 4 groups of 12 eyes. In each group, 3 eyes were assigned to a treatment subgroup, each receiving a different injection-control, bevacizumab, b-PEG, and b-PLGA. In all eyes, laser photocoagulation was used to rupture Bruch's membrane. In group 1, laser was followed by injection, which was then followed by harvesting the rats to assess the CNV area. All 3 steps were separated by a 2-week interval. In groups 2, 3, and 4, injection preceded laser photocoagulation by a variable interval and all rats were harvested 2 weeks postlaser treatment. In group 2, laser and injection were separated by 2 weeks. In group 3, laser followed injection by 4 weeks. In group 4, laser followed injection by 6 weeks. The CNV area was measured for each subgroup and compared against its control. Pairwise comparisons were conducted to assess for statistically significant differences between subgroups.All subgroups in groups 1, 2, and 4 showed statistically significant reduction of CNV area (P0.05). In group 3, the b-PEG and b-PLGA subgroups showed a 9.0% (P=0.384) and 20.3% (P=0.077) reduction in CNV area versus control, whereas there was no reduction in CNV area in the bevacizumab subgroup. However, this was not found to be statistically significant. In group 4, b-PEG was more effective than bevacizumab and b-PLGA.The reduction in CNV area in all treatment subgroups, with the exception of those in group 3, suggests successful creation of the 2 bevacizumab formulations while retaining its active antiangiogenic properties. Further studies varying in dosages and timing of injection and laser are needed to evaluate the formulations' long-acting efficacy.

PURPOSE: To report a patient with an initial presentation of optic disk edema secondary to Propionibacterium acnes endophthalmitis. METHODS: Interventional case report. The patient had surgery and treatment related to endophthalmitis. Nine months after cataract surgery with posterior chamber lens implant, a 79-year-old man receiving topical corticosteroids in the same eye presented with best-corrected visual acuity of 20/60, a superior visual field defect, and optic nerve edema without intraocular inflammation. One year postoperatively, the eye presented a further decrease in best-corrected visual acuity, and a dense white plaque was noted on the posterior capsule. RESULTS: One year postoperatively, a partial capsulectomy with vitrectomy and injection of intravitreal antibiotics was performed. Hematoxylin and eosin stain of the posterior capsule plaque revealed gram-positive coccobacilli characteristic of P. acnes . CONCLUSION: Propionibacterium acnes endophthalmitis may present after cataract surgery with intraocular lens implant with decreased vision, optic disk edema, and a visual field defect.

To report the rate of intraocular pressure (IOP) elevation associated with repeated intravitreal injections of antivascular endothelial growth factor (VEGF) agents and to determine if a pre-existing diagnosis of glaucoma is a risk factor for this phenomenon.The charts of 215 eyes undergoing intravitreal injection with anti-VEGF agents for wet age-related macular degeneration (AMD) were retrospectively examined with respect to frequency of injections, number of injections and changes in IOP. Data were analysed independently for two groups (1) pre-existing glaucoma and (2) no history of glaucoma.Of the 215 eyes receiving injections with bevacizumab and/or ranibizumab, 6% (n=13) had sustained IOP elevation requiring medical or laser interventions. Of the eyes receiving only bevacizumab, 9.9% (10/101) had sustained elevated IOP, while 3.1% (3/96) of eyes receiving only ranibizumab experienced increases (p=0.049). Patients with pre-existing glaucoma experienced higher rates of elevated IOP when compared with patients without pre-existing glaucoma (33% vs 3.1% respectively; p0.001). The glaucoma subgroup had a lower median number of injections (6; interquartile range 5-10) compared with the non-glaucoma group (9.5; interquartile range 6-13.7; p=0.031).The incidence of sustained elevated IOP in patients receiving intravitreal anti-VEGF injections is significant. Additionally, these data suggest the possibility of a heightened risk for further elevation of IOP in patients with pre-existing glaucoma who receive either bevacizumab or ranibizumab. Prospective studies are needed to verify these results and better understand the implications of these findings.

The antivascular endothelial growth factor agents ranibizumab and bevacizumab are used to treat ocular neovascular diseases. There have been recent reports of sustained elevation of intraocular pressure after use of either agent, which we hypothesize could be because of high-molecular-weight aggregates.Enzyme-linked immunosorbent assay, size exclusion chromatography, and polyacrylamide gel electrophoresis were used to analyze repackaged bevacizumab syringes obtained from three outside compounding pharmacies and samples obtained directly from the original vial. Microflow imaging was used to examine particulate material within samples.All syringes contained statistically similar amounts of protein, consisting of immunoglobulin (IgG) heavy and light chains (polyacrylamide gel electrophoresis). However, two of the three compounding pharmacies' batches had significantly less functional IgG in the solution (enzyme-linked immunosorbent assay). Additionally, the compounding pharmacies with the lowest IgG ( approximately 50%) also contained 10-fold the number of micron-sized particulate matter as measured by microflow imaging.There are significant differences in IgG concentration measured from repackaged bevacizumab syringes. A trend exists for an increase in micron-sized protein aggregates with the decrease in IgG concentration. Large particulate matter within some samples may lead to obstruction of aqueous outflow and subsequent elevation in intraocular pressure. Additional studies are warranted to explore these findings.

Background Sclopetaria is a rare ophthalmic finding in trauma Case Presentation This is a report of a patient who developed macular holes from sclopetaria induced by indirect trauma. A 22-year-old male, suffered a gunshot wound that passed behind his eyes, resulting in bilateral macular hole formation Conclusion To our knowledge, this is the first reported case in which trauma posterior to the globes caused bilateral macular hole formation

Anti-vascular endothelial growth factor agents are frequently used to treat a variety of ocular neovascular diseases. While agents like bevacizumab and ranibizumab appear to be safe and effective, there have been reports of severe intraocular inflammation as well as sustained elevation of intraocular pressure (IOP) after single or multiple intravitreal injections of these protein-based therapeutics. The true mechanism leading to inflammation and/or sustained spikes in IOP remains unknown. We report a patient with sustained IOP elevation and kerato-precipitates on the trabecular meshwork after multiple injections of both bevacizumab and ranibizumab. We propose that monomer antibodies, aggregated proteins, or other high molecular weight molecules might lead to inflammation in the trabecular meshwork and subsequent elevation in IOP.

Background and Objective: To compare subfoveal choroidal thickness (SFCT) in normal patients and those with known ocular pathology using spectral domain optical coherence tomography (SD-OCT). Patients and Methods: This retrospective, observational case series was conducted at a tertiary care center where 194 consecutive eyes from 102 patients were imaged. Patients were not included or excluded based on presence or absence of pathology. One masked observer imaged the choroid and a second masked observer measured SFCT. Multivariate analysis was used and a statistical model created to analyze the changes in SFCT induced by age, diabetic retinopathy, glaucoma, wet and dry age-related macular degeneration, and other posterior pole pathology. Results: The mean SFCT of the 194 eyes studied was 246.59 ± 93.17 μm with a mean age of 55.50 ± 19.70 years. A strong negative relationship was found between age and SFCT (R 2 = 0.42), with an average 3.09-μm decrease in SFCT per additional year of age. Subgroup analysis demonstrated that patients with diabetic retinopathy, wet or dry age-related macular degeneration, and glaucoma all had SFCT measurements that were statistically significantly less than those of normal patients. However, when regression analysis was used to control for age, this difference was no longer significant. Conclusion: No differences were found in SFCT in patients with glaucoma, macular degeneration, or diabetic retinopathy compared to eyes lacking pathology when age was counted as a confounding variable. Age has a strong inverse relationship with SFCT, independently confirming prior studies and creating a foundation for more research on the relationship between ocular pathology and choroidal thickness.

Age-related macular degeneration (AMD) affects14 million individuals worldwide. Although 90% of patients with AMD have the dry form, neovascular AMD accounts for the vast majority of patients who develop legal blindness. Until recently, few treatment options existed for treatment of neovascular AMD. The advent of anti-VEGF therapy has significantly improved the safe and effective treatment of neovascular AMD. In addition to two anti-VEGF drugs currently in widespread use, ranibizumab and bevacizumab, a number of medications that interrupt angiogenesis are currently under investigation. One promising new drug is aflibercept (VEGF Trap-Eye), a fusion protein that blocks all isoforms of VEGF-A and placental growth factors-1 and -2.To review the current literature and clinical trial data regarding VEGF Trap-Eye for the treatment of neovascular AMD.Literature review.VEGF Trap-Eye is a novel anti-VEGF therapy, with Phase I and II trial data indicating safety, tolerability and efficacy for the treatment of neovascular AMD. Two Phase III clinical trials (VIEW-1 and VIEW-2) comparing VEGF Trap-Eye to ranibizumab are currently continuing and will provide vital insight into the clinical applicability of this drug.

This retrospective case series reports sustained elevation of intraocular pressure (IOP) after single or repeated intravitreal injections of bevacizumab (Avastin; Genentech, San Francisco, CA) for wet age-related macular degeneration (AMD). All six cases experienced significant and sustained elevation in IOP after single or repeated intravitreal injections of bevacizumab. Initiation or advancement of IOP-lowering therapy was required in all cases. The results support the need for further studies investigating the incidence of this potential side effect and the need for close long-term surveillance of IOP after injection of bevacizumab, particularly in patients with glaucoma or suspected glaucoma. Future in vitro and in vivo studies are needed to better understand the reasons for this observed phenomenon. [Ophthalmic Surg Lasers Imaging 2009;40:293-295.]

Although others have noted a correlation between grating and recognition acuities (RA) when both tests are performed on the same day, the value of preferential looking (PL) in predicting eventual visual outcome has not been studied. PL acuities of 64 preverbal patients considered at risk of amblyopia were measured. When these children became verbal, their visual acuities were determined using standard recognition acuity tests. Based on intervening amblyopia treatment between PL and RA measures, 40 patients were designated the minimal treatment group (MTG) and 24 the intensive treatment group (ITG). Chi-square analysis for the MTG showed agreement (P less than .005) between PL and RA in identifying better, equal, and worse eyes. Interocular ratios of PL and RA were significantly correlated for the MTG (P less than .001), but not for the ITG. Monocularly, a consistent correlation between PL and RA was not found. Our data suggest that PL is predictive of recognition acuity in patients whose visual acuity was expected to remain stable.

Objective To determine whether intravitreal infliximab can inhibit the growth of choroidal neovascularization (CNV) in an animal model of age-related macular degeneration. Methods Twenty-four brown Norway rats received 6 argon laser lesions of sufficient power to rupture the Bruch membrane in each eye. The right eye received a single intravitreal infliximab injection of 0.15 mg/mL, 1.5 mg/mL, or 15 mg/mL. The left eye received an injection of balanced saline solution. The animals were then euthanized at day 30, the eyes were enucleated, and the amount of CNV was quantified with digital analysis software. Results Intravitreal infliximab inhibited CNV growth in the rat laser-trauma model in a dose-response manner. In the 1.5-mg/mL group, there was an 11% reduction in CNV growth ( P = .01). In the 15-mg/mL group, CNV growth was decreased by 68% ( P Conclusions Infliximab can inhibit CNV in a rat laser-trauma model, implicating its target cytokine tumor necrosis factor α in the angiogenic stimulus for CNV. Suppression of inflammatory cytokines may prove to be another therapeutic target in the treatment of exudative macular degeneration. Clinical Relevance This study demonstrates in a model of macular degeneration an antiangiogenic effect of intravitreal infliximab, which provides a rationale for future human studies.

Herein a new surgical technique used during pars plana vitrectomy with internal limiting membrane peeling for macular hole surgery is reported. Perfluorocarbon liquid is used to tamponade the macular hole in order to prevent indocyanine green contact with the retinal pigment epithelium.

To report the occurrence of a full thickness macular hole in association with idiopathic parafoveal telangiectasia.Observational case report.A 60-year-old female with a history of bilateral idiopathic parafoveal telangiectasia presented with acute complaints of decreased vision and metamorphopsia in her right eye. The patient's retinal examination was significant for idiopathic parafoveal telangiectasia bilaterally, and a new, full-thickness macular hole in the right eye which was confirmed by optical coherence tomography.Full-thickness macular hole formation may occur in conjunction with idiopathic parafoveal telangiectasia, which has not been reported to date.

To evaluate the quality of digital retinal images taken by three photographers with different levels of photographic training, using a non-mydriatic fundus camera.This study compares 45-degree digital retinal images taken with a non-mydriatic fundus camera by three different photographers with different levels of photographic training: (I) A professional ophthalmic photographer with 20 years of experience; (2) a non-professional photographer with 2 days of photographic training and experience with 50 patients; (3) a non-professional photographer with 1 hour of photographic training and experience with 10 patients. The quality of the photographs was evaluated by the consensus of two retina specialists.Sixty-four (64) eyes of 33 subjects were imaged by the three photographers for a total of 192 images. Thirty-four eyes were photographed in the non-dilated state. The trained ophthalmic photographer and the two non-professional photographers did not have statistically significant differences in image quality based on the image evaluations. (Chi-square P-value: 0.57). This finding was consistent for eyes in both the non-dilated and dilated state.Fundus image quality for images taken with a non-mydriatic camera were not significantly different among three photographers with different levels of training.

Bevacizumab (Avastin; Genentech Technology, Inc., South San Francisco, CA) is a recombinant human monoclonal antibody that inhibits endothelial cell growth and subsequent vascularization. It was approved for intravenous (IV) treatment of metastatic colorectal cancer by the United States Food and Drug Administration (FDA) in 2004 and subsequently has been approved for IV treatment of non–small cell lung cancer, metastatic breast cancer, glioblastoma, and metastatic kidney cancer. Because of its antivascular activity, bevacizumab has also been used by ophthalmologists for the off-label treatment of wet age-related macular degeneration (AMD). This practice has grown rapidly because repackaged bevacizumab has been very effective in treating AMD1 and because the cost per dose of bevacizumab is substantially lower than that of ranibizumab (Lucentis; Genentech), which is an FDA approved anti-VEGF agent specifically packaged and sold for the treatment of wet AMD.1 The apparent safety and efficacy of intravitreal bevacizumab have been supported by published peer-reviewed reports2–5 and have led the National Eye Institute (NEI) to undertake a large randomized double-masked multicenter clinical trial (Comparison of AMD Treatments Trials [CATT]) to compare bevacizumab with ranibizumab.6 However, reports of sustained elevation of intraocular pressure (IOP) and inflammation after the intravitreal use of bevacizumab and ranibizumab have been increasing.7–13 Recently, we proposed that some increases in IOP could be due to particulate matter present in bevacizumab, which for off-label use is typically repackaged in plastic syringes.14 In support of this hypothesis, our investigation documented that there were both protein aggregates and particles ≥1 μm in repackaged bevacizumab obtained from three external compounding pharmacies. Many factors (e.g., storage time, type of syringe, freeze-thawing, and mechanical shock during shipping) that could affect particle and protein aggregate levels and sizes in repackaged bevacizumab have not been investigated. Furthermore, determining the ranges of values for these critical product characteristics in samples purchased from different external compounding pharmacies is important for the field. In the present study, we addressed these problems with repackaged bevacizumab. First, we quantified the levels of subvisible particles and protein aggregates in bevacizumab in plastic syringes purchased from four external compounding pharmacies. Second, we performed controlled laboratory experiments with bevacizumab repackaged in the same types of plastic syringes as those used by the external compounding pharmacies. We tested the effects of storage at room temperature (with and without exposure to light), −20°C, and 4°C on particle counts and protein aggregates and the effects of repetitive freeze-thawing. In addition, we studied the potential for freeze-thawing of samples in shipping containers used by the external compounding pharmacies and the effects of mechanical shock due to handling mimicking that occurring during shipping. We used a particle characterization technique (MicroFlow Imaging [MFI]; Brightwell Technologies, Ottawa, ON, Canada) to count and size particles ≥1 μm and size-exclusion high-performance liquid chromatography (SE-HPLC) to quantify levels of monomeric and aggregated bevacizumab. Also, we conducted analyses and experiments that documented that most of the particles were due to silicone oil microdroplets. Finally, for comparison to results with repackaged bevacizumab, we also quantified the subvisible particles present in ranibizumab samples. In this article, we report that bevacizumab repackaged in plastic syringes was contaminated by silicone oil microdroplets. Freeze-thawing and mechanical shock can further degrade the product and increase levels of particle contaminants. Although we cannot directly link silicone oil contaminants and bevacizumab aggregates with sustained elevation of IOP and inflammation at this time, based on current studies, mishandling of repackaged bevacizumab should be and can be avoided.

Jeffrey Olson, Behnaz Rouhani, Naresh MandavaRocky Mountain Lions Eye Institute, University of Colorado Health Sciences Center, Department of Ophthalmology, Denver, CO, USAAbstract: Sub-Tenon’s injection of triamcinolone was performed in the right eye of a patient with bilateral Purtscher’s-like retinopathy after childbirth. The response of macular edema to local triamcinolone was investigated with optical coherence tomography. Five weeks following the injection, optical coherence tomography improvement was seen following unilateral sub-Tenon’s triamcinolone injection.Keywords: Purtscher’s-like retinopathy; triamcinolone; post-partum decreased vision

We present a case of ocular deviation and diplopia that developed 9 months after monocular excimer laser photorefractive keratectomy. In this case, decompensation occurred because of a breakdown of fusion at distance. We suggest a cover test to assess the presence of significant phorias in all candidates for refractive surgery procedures.