Cardiovascular and Mortality Risk with Intravitreal Vascular Endothelial Growth Factor Inhibitors in Patients with Diabetic Retinopathy.

OBJECTIVE: To investigate the cardiovascular (CV) safety associated with intravitreal anti-VEGF injections (IAVIs) in patients with diabetic retinopathy (DR). DESIGN: Population-based cohort study using Medicare and 2 commercial insurance claims databases in the United States from January 2009 to December 2017. SUBJECTS: Patients with DR aged ≥ 18 years in whom treatment with either IVAIs or laser procedure or intravitreal steroid injections was initiated. METHODS: We estimated the propensity score (PS) using multivariable logistic regression models, including 85 baseline covariates and PS-matched patients in a 1:1 ratio. We estimated the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on prior history of CV events were also conducted. MAIN OUTCOME MEASURES: A composite CV outcome of myocardial infarction (MI) or stroke, its individual components, and all-cause mortality in 180 and 365 days after treatment initiation. RESULTS: We identified 61 508 PS-matched patients in a 1:1 ratio in whom either IVAIs or laser or steroid treatment was initiated. Compared with laser or steroid treatment, IAVIs were not associated with an increased risk of the composite CV outcome (HR, 0.95; 95% CI, 0.83-1.09), MI (HR, 0.93; 95% CI, 0.76-1.13), or stroke (HR, 0.98; 95% CI, 0.80-1.19) or the risk of all-cause mortality (HR, 1.25; 95% CI, 0.97-1.62) at 180 days of follow-up. At 365 days, the risk of the composite CV outcome, stroke, and MI remained similar between the 2 groups, although the risk of all-cause mortality was increased with IAVIs (HR, 1.35; 95% CI, 1.14-1.60). The subgroup analysis showed that the risk of all-cause mortality was increased in patients with a prior history of CV events. CONCLUSIONS: Among > 60 000 patients with DR, those who received IAVIs had a risk of CV events similar to those who received laser or steroid treatment. However, the risk of all-cause mortality was higher in patients who received IAVIs for DR.

Risk of Cataract Surgery and Age-Related Macular Degeneration After Initiation of Denosumab vs Zoledronic Acid for Osteoporosis: A Multi-Database Cohort Study.

BACKGROUND AND OBJECTIVE: There is a relative lack of head-to-head comparisons of denosumab against other osteoporosis drugs on safety. We aimed to explore ocular outcomes in patients with osteoporosis initiating denosumab vs zoledronic acid. METHODS: We conducted a cohort study using claims data (2010-15) from two large US commercial insurance databases including patients with osteoporosis who were aged 50 years or older and initiators of denosumab or zoledronic acid. The primary outcomes were (1) receipt of cataract surgery and development of (2) wet age-related macular degeneration and (3) dry age-related macular degeneration within 365 days after initiation of denosumab vs zoledronic acid. Propensity score fine stratification and weighting were used to control for potential confounding, and we calculated the incidence rate and hazard ratio for each outcome in the cohorts. The estimates from the two databases were combined with a fixed-effects model meta-analysis. RESULTS: The study cohort included 50,821 denosumab and 67,471 zoledronic acid initiators. In the propensity score-weighted analysis, compared to zoledronic acid use, denosumab was associated with a modestly decreased risk of undergoing cataract surgery (hazard ratio 0.91; 95% confidence interval 0.85-0.98) but not with the risk of wet age-related macular degeneration (hazard ratio 1.29; 95% confidence interval 0.99-1.70) or dry age-related macular degeneration (hazard ratio 1.03; 95% confidence interval 0.98-1.09). CONCLUSIONS: In this large population-based cohort study of 118,292 patients with osteoporosis, initiation of denosumab was associated with a modestly decreased risk of cataract surgery vs zoledronic acid. The risk of age-related macular degeneration was similar between the two drugs.

Risk of Uveitis in Patients With Inflammatory Bowel Disease on Immunosuppressive Drug Therapy.

Background: Inflammatory bowel disease (IBD) patients may develop anterior uveitis. Methods: An observational cohort of IBD patients followed new users of (1) tumor necrosis factor inhibitor versus nonbiologic agents or (2) adalimumab versus infliximab until occurrence of anterior uveitis or treatment change/discontinuation. Cox-proportional hazards models estimated hazard ratios in propensity score-matched cohorts of Crohn disease or ulcerative colitis patients. Results: No statistically significant differences in the risk of uveitis were observed between initiators of nonbiologics and tumor necrosis factor inhibitor. Effect estimates for adalimumab versus infliximab were highly imprecise due to limited outcomes. Conclusions: Uveitis risk was not different between IBD patients treated with immunosuppressives.

Characterization of Epiretinal Proliferation in Full-Thickness Macular Holes and Effects on Surgical Outcomes.

PURPOSE: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that classically is associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterized macular hole-associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. DESIGN: Multicenter, interventional, retrospective case-control study. PARTICIPANTS: Consecutive eyes that underwent surgery for FTMH with a minimum of 12 months follow-up. METHODS: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane (ILM) peeling. Spectral-domain OCT imaging was obtained before and after surgery. MAIN OUTCOME MEASURES: Improvement in visual acuity and single-surgery hole closure rates in eyes with, versus without, MHEP at 12 months. RESULTS: Seven hundred twenty-five charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) showed MHEP. Patients with FTMH and MHEP were older (P < 0.002) and more often men (P = 0.001), and showed more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). Twelve months after surgery, FTMH with MHEP patients showed significantly less improvement in visual acuity (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with 1 surgery compared to FTMH without MHEP (26.7% vs. 4.8%; P = 0.002]). Peeling the ILM was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariate testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031) and for single-surgery nonclosure (P = 0.009) and that ILM peeling improved single-surgery closure rates (P = 0.026). CONCLUSIONS: We found that FTMH with MHEP showed poorer anatomic and visual outcomes after vitrectomy compared with FTMH without MHEP. Internal limiting membrane peeling was associated with improved closure rates and should be considered when MHEP is detected before surgery.

Closure of Macular Hole Associated With Extreme High Myopia After Conventional Vitrectomy With ILM Peeling.

Macular hole associated with high myopia (MH-HM) and macular hole-associated retinal detachment (MH-RD) are two conditions found in eyes with pathologic myopia that often have poor postoperative outcomes. A discrepancy in size between the stretched retina and the posteriorly expanded sclera is a major factor in the pathogenesis. The authors report a case comprising both types of maculopathy, one in each eye. The eye with the MH-HM (right eye) represents the longest axial length ever reported to have successful macular hole closure by any technique. The authors conclude that traditional surgery can be an adequate treatment for such a challenging condition. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e99-e101.].

Comparison of Progression to Advanced Stage between Polypoidal Choroidal Vasculopathy and Age-Related Macular Degeneration in Korea.

PURPOSE: To compare the rate of progression to advanced stage in the fellow eye of patients with typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in a South Korean cohort. DESIGN: This is an observational, consecutive retrospective case series. PARTICIPANTS: Patients with unilateral advanced stage AMD (n = 288; 180 typical AMD patients and 108 PCV patients). METHODS: Clinical assessment included detailed eye examination, including fundus photography, fluorescein angiography, and indocyanine green angiography. MAIN OUTCOME MEASURES: Five-year progression rate to advanced stage in the fellow eye based on initial Age-Related Eye Disease Study (AREDS) score and the correlation between the initial AREDS score and progression to advanced disease in the fellow eye according to types of AMD. RESULTS: Five-year progression to advanced disease in the fellow eye was similar between typical AMD and PCV cases (11.1% vs. 14.8 %, respectively; P = 0.466, log-rank test). Among patients with initial AREDS score of 2 (normal macula or small drusen on the fellow eye), a higher proportion of patients progressed to advanced disease in the PCV group compared with typical AMD patients (10.4% vs. 2.4 %, respectively; P = 0.0042, log-rank test). Initial AREDS score correlated significantly with progression of the fellow eye to advanced stage in the typical AMD group, after adjusting for age, gender, and other comorbidities (hazard ratio [HR], 9.5; 95% confidence interval [CI], 2.80-32.12; P = 0.0003). However in the PCV group, initial AREDS score did not correlate with progression to advanced stage in the fellow eye (HR, 1.84; 95% CI, 0.83-4.05; P = 0.13). CONCLUSIONS: Unlike typical AMD, PCV progresses without typical features such as drusen or pigmentary abnormality. Baseline AREDS score was less likely to predict progression of the fellow eye to advanced-stage disease in PCV compared with typical AMD. Therefore, the globally recognized risk-scoring AREDS system may not be applicable in Asia, where PCV is a prevalent subtype of AMD.

Choristomatous Respiratory Cyst Restricted to the Upper Eyelid.

A 79-year-old man underwent excision of an upper eyelid mass that had been enlarging for 3 months. Histopathologic evaluation demonstrated a cyst lined by pseudostratified columnar epithelium with myriad goblet cells and cilia, and immunostaining revealed cytokeratins indicative of a respiratory origin. This rare condition, the first described exclusively in an eyelid, arises either from a congenital embryologic respiratory epithelial ectopia or the displacement of mature sinus mucosa following trauma or chronic sinus disease. The current case lacked any signs or symptoms of sinus disease or a history of trauma.

Caruncular dacryops.

PURPOSE: To report a case of caruncular dacryops in a 58-year-old man that was excised in its entirety and to offer an immunohistopathologic analysis. METHODS: Sections stained with hematoxylin and eosin, periodic acid-Schiff, and Grocott methenamine silver (the latter 2 for identification of mucus) were evaluated, and immunohistochemical investigations were performed using cytokeratin (CK) 7, CK14, CK17, and smooth muscle actin. RESULTS: Histopathologic examination revealed a cystic dilation of the lacrimal gland ducts containing secretory globules. The ducts were composed of double-layered cuboidal epithelium with rare scattered goblet cells and interspersed prominent lobules of lacrimal gland tissue, diagnostic of dacryops. Immunohistochemistry of cystic ducts demonstrated a CK profile identical to that of the conjunctiva including the absence of a myoepithelium. CONCLUSIONS: This is the first case of an intact caruncular lacrimal ductal cyst (dacryops). A previous report documented a spontaneously collapsed cyst with extrusion of secretory globoid bodies into extracellular space that elicited a foreign body giant cell response.

Etanercept, a widely used inhibitor of tumor necrosis factor-α (TNF-α), prevents retinal ganglion cell loss in a rat model of glaucoma.

BACKGROUND: Visual loss in glaucoma is associated with pathological changes in retinal ganglion cell (RGC) axons and a slow decline in the RGC population. Age and elevated intraocular pressure (IOP) are the main risk factors for glaucomatous loss of vision. Several studies have implicated the proinflammatory cytokine tumor necrosis factor-α (TNF-α) as a link between elevated IOP and RGC death, but the cellular source of TNF-α and its causative role in RGC death remain uncertain. Here, using a rat model of glaucoma, we investigated the source of elevated TNF-α and examined whether Etanercept, a TNF-α blocker that is in common clinical use for other indications, is protective against RGC death. METHODOLOGY/PRINCIPAL FINDINGS: Episcleral vein cauterization (EVC) caused intraocular pressure (IOP) to be elevated for at least 28 days. IOP elevation resulted in a dramatic increase in TNF-α levels within a few days, axonal degeneration, and a 38% loss of RGCs by 4 weeks. Immunostaining coupled with confocal microscopy showed that OHT induced robust induction of TNF-α in Iba-1-positive microglia around the optic nerve head (ONH). Despite persistent elevation of IOP, Etanercept reduced microglial activation, TNF-α levels, axon degeneration in the optic nerve, and the loss of RGCs. CONCLUSIONS/SIGNIFICANCE: Ocular hypertension (OHT) triggers an inflammatory response characterized by the appearance of activated microglia around the ONH that express TNF-α. Blocking TNF-α activity with a clinically approved agent inhibits this microglial response and prevents axonal degeneration and loss of RGCs. These findings suggest a new treatment strategy for glaucoma using TNF-α antagonists or suppressors of inflammation.

Tauroursodeoxycholic acid (TUDCA) protects photoreceptors from cell death after experimental retinal detachment.

BACKGROUND: Detachment of photoreceptors from the underlying retinal pigment epithelium is seen in various retinal disorders such as retinal detachment and age-related macular degeneration and leads to loss of photoreceptors and vision. Pharmacologic inhibition of photoreceptor cell death may prevent this outcome. This study tests whether systemic administration of tauroursodeoxycholic acid (TUDCA) can protect photoreceptors from cell death after experimental retinal detachment in rodents. METHODOLOGY/PRINCIPAL FINDINGS: Retinal detachment was created in rats by subretinal injection of hyaluronic acid. The animals were treated daily with vehicle or TUDCA (500 mg/kg). TUNEL staining was used to evaluate cell death. Photoreceptor loss was evaluated by measuring the relative thickness of the outer nuclear layer (ONL). Macrophage recruitment, oxidative stress, cytokine levels, and caspase levels were also quantified. Three days after detachment, TUDCA decreased the number of TUNEL-positive cells compared to vehicle (651±68/mm(2) vs. 1314±68/mm(2), P = 0.001) and prevented the reduction of ONL thickness ratio (0.84±0.03 vs. 0.65±0.03, P = 0.002). Similar results were obtained after 5 days of retinal detachment. Macrophage recruitment and expression levels of TNF-a and MCP-1 after retinal detachment were not affected by TUDCA treatment, whereas increases in activity of caspases 3 and 9 as well as carbonyl-protein adducts were almost completely inhibited by TUDCA treatment. CONCLUSIONS/SIGNIFICANCE: Systemic administration of TUDCA preserved photoreceptors after retinal detachment, and was associated with decreased oxidative stress and caspase activity. TUDCA may be used as a novel therapeutic agent for preventing vision loss in diseases that are characterized by photoreceptor detachment.